Reproductive Physiology
By; T/berhan H.
MSc. Medical Physiology
2
 Process of;
◦ Procreation: maintenance of ones species
◦ Recreational and Relational
 Two types of reproduction
1. Asexual; Binary fission, budding, .....
2. Sexual; involves copulation of male and a female of the
same species
Reproduction
3
 Sexual reproduction results in genetic diversity due to
 Shuffling of genes
 Crossing-over in meiosis and
 Fertilization
 Sexual reproduction produces new individual that is
genetically different from it’s parents
 So new combinations of genes occur in each generation.
….cont
4
 During 7th
week of IUL, bi-potential primordial germ cells
(primitive gonadal cells) appears
 The embryo has a primitive female and male genital tracts
called the Mullerian and Wolffian duct respectively.
 In the absence of Y-chromosome, these germ cells
develop into ovaries
 In the presence of Y-chromosome, the primitive gonadal
cells develop into testis
Development and differentiation of reproductive
organs and tracts
5
 In the absence of functioning testis
◦ The Wolffian duct regresses and
◦ The Mullerian duct develops into the female internal genitalia; the
fallopian tube, uterus and upper 2/3 of vagina
◦ The urogenital slit remains open and the female external genitalia
develops.
 In the presence of functioning testis
◦ Wolffian duct develops into the male internal genitalia, ie,
epididymis, vas deferens, seminal vesicles and prostate
◦ Urogenital slit is closed and male external genitalia (penis and
scrotum) develops
6
7
THE MALE REPRODUCTIVE
PHYSIOLOGY
Composed of;
 Gonads;
◦ Testes
 Reproductive tract;
◦ Epididymis
◦ Vas deference
◦ Urethra
 External genitalia
◦ Penis;
 Corpora cavernosa
 Corpora spongiousum
 Accessory glands
◦ Prostate
◦ Seminal vessicles
◦ Bulbourethral glands
Functions;
◦ Production of sperm (spermatogenesis)
◦ Delivery of sperm to female
9
Male reproductive system
10
Seminiferous tubule
 There are about 900 coiled
seminiferous tubules in both testis
 Each averaging more than one-half
meter
 Site of sperm production
Epididymis
 Coiled tube which is about 6 meters
long
 The next structure where sperm is
emptied and
 Site of sperm storage
11
Male reproductive functions can be divided into three
major subdivisions:
1. Spermatogenesis - formation of sperm cells
2. Performance of the male sexual act
3. Production of hormones
12
At embryonic life,
 Primordial germ cells migrate into the testes and
 Become immature germ cells called spermatogonia, which
 Lie in inner surfaces of the seminiferous tubules
During puberty,
 Spermatogonia begin to undergo mitotic division and continually
proliferate and differentiate to form sperm
 It begins at an average of 13 years of age and
 Continues throughout life
 But decreases markedly in old age
 It happens as a result of stimulation by gonadotropic hormones from
anterior pituitary
13
SPERMATOGENESIS
 Serious of repeated mitotic cell division happens first
 During these cell divisions spermatogonia migrate toward
the central lumen of the seminiferous tubule along with
Sertoli cells and mature to become primary spermatocytes
14
STEPS OF SPERMATOGENESIS
 Then two successive meiotic division happens
 Which are Meiosis I (secondary spermatocyte) and
Meiosis II (spermatids)
 Spermatids are progressively modified to become
spermatozoa (sperm)
 Each spermatids finally have haploid (23) chromosomes
due to the meiotic division
 The whole process takes about 74 days
15
….cont
 Among the 23 pairs of chromosomes in each
spermatogonium, one pair is composed of sex
chromosomes (X and Y chromosomes)
 During meiotic division each strand of the sex
chromosome goes to one spermatid
 This determine the sex of the eventual offspring
16
17
18
Testosterone;
 Secreted by the Leydig cells
 Essential for growth and division of the testicular
germinal cells - the first stage of sperm cell formation
Luteinizing hormone;
 Secreted by the anterior pituitary gland
 Stimulates the Leydig cells to secrete testosterone
19
Hormones that stimulate
Spermatogenesis
Follicle-stimulating hormone;
 Another hormone from anterior pituitary gland,
 Stimulates the Sertoli cells
Estrogens;
 Formed from testosterone by the Sertoli cells when
stimulated by FSH
 Believed to be essential for spermiogenesis
20
Growth hormone ;
 Important in controlling metabolic functions of the
testes, as well as
 It promotes early division of the spermatogonia
 In its absence, spermatogenesis is severely deficient or
absent, thus causing infertility.
21
 Sperm cell removed from the seminiferous tubules
and/or early portions of the epididymis are non-
motile and cannot fertilize an ovum.
 In the epididymis sperm cells continue to undergo
some developmental stages and continue to get
matured, but
 Still several inhibitory proteins in the epididymal fluid
prevent final motility until after ejaculation.
22
Maturation of Sperm in the Epididymis
 Before ejaculation, sperm cells are not motile and can’t
fertilize an ovum
 Full motility is achieved after ejaculation
 Ejaculated sperm cells also have special nutrient fluid
(from Sertoli cells and the epithelium of the epididymis)
 This fluid contains hormones (like testosterone and
estrogens), enzymes, and special nutrients that are
essential for sperm nutrition
23
 Each day about 120 million sperm cells are produced
on both tests.
 Majority of these sperm are stored in the epididymis,
but
 Small quantity is stored in the vas deferens
 Can be stored maintaining their fertility for at least a
month
 During this stay, these are kept in a deeply suppressed,
inactive state by multiple inhibitory substances
24
Storage of Sperm in the Testes
 Matured fertile sperm can move on fluid medium at
velocities of 1 to 4 mm/min.
 The activity of sperm is greatly enhanced in a neutral
and slightly alkaline medium
 But, it is greatly depressed in a mildly acidic medium.
 Strong acidic medium can cause the rapid death of
sperm.
25
Physiology of the Mature Sperm
 Increasing temperature increases the activity of sperm
but so does the rate of metabolism,
 But in such conditions the life span of the sperm cells
is shorter and
 Ejaculated sperm in the female genital tract can stay
only for 1 to 2 days.
26
 Matured sperm have head and tail
Head
 The head contains thin cytoplasmic and cell membrane
layer and mainly condensed with nucleus of the cell
 The head on it’s outside anterior 2/3 is covered with a thick
cup called acrosome, which is formed from Golgi apparatus
27
 The acrosome contains two main enzymes
 Hyaluronidase enzyme; which can digest proteoglycan
filaments of tissues and
 Powerful proteolytic enzymes; which can digest
proteins
 These enzymes play important roles in allowing the
sperm to enter the ovum and fertilize it
28
Tail(flagellum)
 Is the other part of matured spermatozoa which has three
major components:
1. A central skeleton constructed of 11 microtubules,
collectively called the axoneme (similar to that of cilia)
2. A thin cell membrane covering the axoneme
3. A collection of mitochondria around the axoneme in the
proximal portion of the tail (body of the tail).
29
30
Motility of sperm
 Achieved by the back-and-forth movement of the tail
which results from a rhythmical longitudinal sliding
motion of the anterior and posterior tubules of the
axoneme.
 This process gets it’s energy from ATP, which is
synthesized by the mitochondria
 Normal sperm move in a fluid medium at a velocity of
1-4 mm/min.
31
 Seminal vesicles is lined with a secretory epithelium that
◦ Secretes a mucoid material
◦ With high amount of fructose, citric acid, and other nutrient
substances
◦ It also contains large quantities of prostaglandins and fibrinogen
 Seminal vesicle empties its contents into the ejaculatory duct
which adds greatly to the bulk of the ejaculated semen, and
 So the fructose and other substances in the seminal fluid are
used as a source of nutrient for the ejaculated sperm
32
FUNCTION OF THE SEMINAL
VESICLES
 Prostaglandins aid fertilization in two ways:
1. It reacts with the female cervical mucus and make it more
receptive to sperm movement
2. It causes backward, reverse peristaltic contractions in the
uterus and fallopian tubes and this help move the ejaculated
sperm toward the ovaries
33
 Prostate gland secretes a thin, milky fluid that
◦ Contains calcium, citrate ion, phosphate ion, a clotting enzyme, and a profibrinolysin.
◦ Is slightly alkaline that helps to neutralize the seminal fluids from the
 Vas deference (due to the presence of citric acid and metabolic end products) and
 Vaginal secretions (pH of 3.5 to 4.0).
 Sperm cell become optimally motile and can fertilize the ovum at pH of 6.0
- 6.5.
 So the slightly alkaline prostatic fluid helps neutralize the acidity of the
other fluids and enhance the motility and fertility of the sperm.
 The average pH of the combined semen is about 7.5, (more than neutralized
by prostatic fluid)
34
FUNCTION OF THE PROSTATE
GLAND
 Semen is the fluid ejaculated during the male sexual
act, which is composed of
◦ Fluid and sperm from the vas deferens (10%),
◦ Fluid from the seminal vesicles (60%),
◦ Fluid from the prostate gland (30%), and
◦ Small amounts from the mucous glands, especially the
bulbourethral glands.
 The bulk of the semen is seminal vesicle fluid, which is
the last to be ejaculated and serves to wash the sperm
through the ejaculatory duct and urethra.
35
SEMEN
Semen has;
 Milky appearance – due to prostatic fluid
 Mucoid consistency – due to fluid from the seminal vesicles and
mucous glands
 Sticky nature - due to clotting enzymes from the prostatic fluid that
cause the fibrinogen of the seminal vesicle fluid to form a weak fibrin
coagulum that holds the semen in the deeper regions of the vagina
 The coagulum then dissolves during the next 15 to 30 minutes because
of lysis by fibrinolysin formed from the prostatic profibrinolysin.
 In the early minutes after ejaculation, the sperm remain relatively
immobile, possibly because of the viscosity of the coagulum.
 As the coagulum dissolves, the sperm simultaneously become highly
motile
36
Life span of sperm;
 For weeks in the male genital ducts
 For only 24 to 48 hours at body temperature
 For several weeks at lowered temperatures, and
 For years when frozen at temperatures below −100°C
37
 Sperm cell can’t fertilize an ovum immediately after ejaculation
b/se the inhibitory factors are still present with the ejaculated
semen
 It needs further changes – “capacitation”
 The basic changes are;
1. The uterine and fallopian tube fluids wash away the various
inhibitory factors that suppress the sperm
2. Sperm swim away from the cholesterol vesicles that it covers
towards the uterine cavity so that the membrane at the head of the
sperm (the acrosome) becomes much weaker and allowing release
of it’s enzymes
38
“Capacitation” of Spermatozoa
3. The membrane of the sperm also becomes much more
permeable to calcium ions, so
 Calcium now enters the sperm in abundance and changes
the activity of the flagellum, giving it a powerful
whiplash motion in contrast to its previously weak
undulating motion.
 In addition, the calcium ions cause changes in the cellular
membrane that cover the leading edge of the acrosome,
making it possible for the acrosome to release its enzymes
rapidly and easily as the sperm penetrates the granulosa
cell mass surrounding the ovum, and even more so as it
attempts to penetrate the zona pellucida of the ovum.
39
 Acrosome of the sperm contains large quantities of hyaluronidase
and proteolytic enzymes.
Hyaluronidase;
 Depolymerizes the hyaluronic acid polymers in the intercellular
cement
 Open pathways between the granulosa cells so that the sperm can
reach the zona pellucida.
The proteolytic enzymes;
 Digest proteins in the structural elements of tissue cells that still
adhere to the ovum.
 Open a penetrating pathway for passage of the sperm head
through the zona pellucida to the inside of the ovum
40
“Acrosome Reaction” and Penetration of
the Ovum
 After a few minutes of the first sperm penetrates the zona
pellucida, calcium ions diffuse inward through the oocyte
membrane and cause multiple cortical granules to be
released by exocytosis from the oocyte into the
perivitelline space.
 These granules contain substances that permeate all
portions of the zona pellucida and prevent binding of
additional sperm, and they even cause any sperm that have
already begun to bind to fall off.
 Thus, almost never does more than one sperm enter the
oocyte during fertilization.
41
Why does only one sperm enter the
Oocyte?
Two important areas of initiation
1. Glans penis; most important source of sensory nerve
signals for initiating the male sexual act
 The glans contains an especially sensitive sensory end-
organ system that transmits into the central nervous
system
 Sexual signals from sensory end-organ pudendal
nerve sacral plexus sacral portion of
spinal cord undefined areas of the brain
42
MALE SEXUALACT
Signals could also come from;
 Outer nearby structures like the anal epithelium, the
scrotum, and perineal structures
 Internal structures, like in the areas of urethra, bladder,
prostate, seminal vesicles, testes, and vas deferens
43
2. Psychic element of sexual stimulation
 Can greatly enhance the ability of a person to perform the sexual
act
 Can even result in nocturnal emissions during dreams, often
called “wet dreams,”
 So it can be initiated by either
◦ Psychic stimulation from the brain or
◦ Actual sexual stimulation from the sex organs, but
◦ Usually it is a combination of both
Integration of the male sexual act in the Spinal Cord
 Male sexual act is mainly integrated in the spinal cord (sacral
and lumbar spinal cord)
44
STAGES OF THE MALE SEXUAL ACT
Penile Erection - Parasympathetic Nerves
 Is the first effect of male sexual stimulation,
 Degree of erection is proportional to degree of stimulation,
 Release of nitric oxide and/or vasoactive intestinal peptide
 Relaxation of the arteries of the penis and the trabecular
meshwork of smooth muscle fibers in the erectile tissue of
the corpora cavernosa and corpus spongiosum
45
 The erectile tissue consists of large cavernous sinusoids that are
normally empty of blood
 But become dilated when arterial blood flows rapidly into them
under pressure while the venous outflow is partially occluded
 The two corpora cavernosa, are surrounded by strong fibrous
coats; therefore,
 High pressure within these sinusoids causes ballooning of the
erectile tissue
 Then the penis becomes hard and elongated – erection
46
47
Lubrication - Parasympathetic NS
 During stimulation, the PNS impulses stimulate the
urethral and bulbourethral glands to secrete mucus.
 This mucus flows through the urethra during
intercourse to aid in lubrication during coitus
 But, most of the lubrication of coitus is provided by the
female sexual organs
 Without adequate lubrication, intercourse causes
grating and painful sensations that inhibit sexual
sensations
48
Emission and Ejaculation – Sympathetic NS
 Final stages of sexual act
 When the sexual stimulus reaches it’s climax,
sympathetic impulses start to be emitted from the reflex
centers of the spinal cord
 It leaves the cord at T12 - L2 and pass to the genital
organs through the hypogastric and pelvic sympathetic
nerve plexuses
49
Emission;
 Begins with contraction of the vas deferens and the ampulla
to cause expulsion of sperm into the internal urethra.
 Then, contractions of the muscular coat of the prostate gland
followed by contraction of the seminal vesicles expel
prostatic and seminal fluid also into the urethra.
 All these fluids mix in the internal urethra with mucus
secreted by the bulbourethral glands to form the semen.
 This all is the process of emission.
50
Ejaculation;
 The filling of the internal urethra with semen elicits
sensory signals that are transmitted through the
pudendal nerves to the sacral regions of the cord,
giving the feeling of sudden fullness in the internal
genital organs.
 These sensory signals further excite rhythmical
contraction of the internal genital organs and cause
contraction of the ischiocavernosus and
bulbocavernosus muscles that compress the bases of
the penile erectile tissue.
51
 These together increases the pressure in the erectile
tissue of the penis, genital ducts and urethra
 This helps “ejaculate” the semen to the exterior -
ejaculation
 At the same time, rhythmical contractions of the pelvic
muscles and some of muscles of the body trunk causes
 Thrusting movements of the pelvis and penis, which
also help propel the semen into the deepest recesses of
the vagina
52
 This entire period of emission and ejaculation is called
the male orgasm.
 At its termination, the male sexual excitement
disappears almost entirely within 1 to 2 minutes and
erection ceases, a process called resolution.
53
Secretion of Testosterone
 The testes secrete several androgens which are also called male sex
hormones
 These including testosterone, dihydrotestosterone, and
androstenedione
 Testosterone is more abundant and considered as the primary testicular
hormone
 But, much of the testosterone is eventually converted into the more
active hormone dihydrotestosterone in the target tissues
54
TESTOSTERONE AND OTHER
MALE SEX HORMONES
 Testosterone is formed by the Leydig cells
 Leydig cells;
◦ Found in the interstices between the seminiferous tubules and
◦ Constitute about 20% of the mass of the adult testes
◦ Are numerous in newborn in the first few months of life and
after puberty
◦ Are less easily destroyed by x-ray or excessive heat
55
 Androgens are also produced elsewhere in the body
besides the testes
1. Adrenal gland
◦ But it doesn’t have significant masculinizing effect
◦ However, in tumorous conditions significant amount may be
produced and cause male secondary sexual characteristics, even
in the female
2. Ovary also produces minute/insignificant quantities of
androgens
 All androgens are steroid and can be synthesized either
from cholesterol or directly from acetyl coenzyme A.
56
 About 97% of testosterone becomes either
◦ Loosely bound with plasma albumin or
◦ More tightly bound with beta globulin and
◦ Circulates in the blood in these states for 30 minutes to several
hours.
 Then it is either transferred to the tissues or degraded into
inactive products that are subsequently excreted
 Much of the testosterone fixed to the tissues is converted
to dihydrotestosterone, especially in certain target organs
57
Metabolism of Testosterone
 The testosterone that does not become fixed to the
tissues is rapidly converted in to other forms mainly by
the liver
 Then excreted either into the gut by way of the liver bile
or into the urine
58
Estrogen production
 Small amounts of estrogens are also formed in the male
(about 1/5th
of non-pregnant female)
 The exact source isn’t known, but the following are the
possible sources:
1. Conversion of testosterone to estradiol by Sertoli cells
2. Formation of estrogen from testosterone and
androstanediol by other tissues (liver)
59
60
 Generally, testosterone is responsible for masculinization of
the body
Functions of Testosterone During Fetal Development
 Is responsible for the development of the male body
characteristics, including the formation of a penis and a
scrotum
 It also helps formation of prostate gland, seminal
vesicles, and male genital ducts
 It also suppresses the formation of female genital
organs.
 Testosterone is the main stimulus for decent of testes
61
FUNCTIONS OF TESTOSTERONE
Effect on Development of Adult Primary and Secondary
Sexual Characteristics
 After puberty, testosterone cause the penis, scrotum,
and testes to enlarge about eightfold before the age of
20 years.
 Causes the secondary sexual characteristics of the male
to develop, starting from puberty
 Also causes growth of hair in different body parts;
pubis, linea alba, face, chest, …
62
 Testosterone causes male pattern baldness
 Testosterone also causes masculine voice (causes
hypertrophy of the laryngeal mucosa and enlargement
of the larynx)
 Testosterone increases thickness of skin and contribute
to the development of acne
 Testosterone increases protein formation and muscle
development
63
 Testosterone increases bone matrix and causes calcium
retention
 Testosterone increases the basal metabolic rate
 Testosterone increases red blood cells
 Effect on electrolyte and water balance
◦ Has a little effect on electrolytes, but still increases
◦ Blood and ECF volume (increases by 5-10% of body wt)
64
 Most of the effects result basically from increased rate of protein formation
 So basically testosterone enters the cell and is converted to
dihydrotestosterone with the action of 5α-reductase
 This in turn binds with cytoplasmic receptor protein and enters the nucleus
 Then it binds with nuclear protein to induce DNA-RNA transcription
 Then RNA concentration increases which progressively rising the cellular
proteins
 The number of DNA also rises increasing the number of cells too
65
BASIC INTRACELLULAR MECHANISM
OF ACTION OF TESTOSTERONE
GnRH;
 Is secreted by neurons in the hypothalamus and released
into the hypothalamic-hypophysial portal vascular system.
 GnRH is then transported to the anterior pituitary gland in
the hypophysial portal blood
 Then it stimulates the release of the two gonadotropins, LH
and FSH
66
CONTROL OF MALE SEXUAL FUNCTIONS BY
HORMONES FROM THE HYPOTHALAMUS AND
ANTERIOR PITUITARY GLAND
 GnRH is secreted for a few minutes at a time once
every 1-3 hours – pulsatile release of GnRH
 It’s secretion is determined by
1) The frequency of these cycles and
2) The quantity of GnRH released in each cycle
 The rate of FSH release is slightly affected by this
pulsatile release of GnRH, rather
 It changes more slowly over a period of many hours in
response to long term changes in GnRH
67
 But, the secretion of LH is also cyclical, which follows
the pulsatile release of GnRH.
 Because of this closer relation between GnRH and LH
secretion, GnRH is also widely called LH-releasing
hormone
68
69
Gonadotropic Hormones: LH and FSH
 These are glycoprotein hormones secreted by the same cells of
anterior pituitary gland, called gonadotropes.
 Almost no LH or FSH are secreted in the absence of GnRH
 Testosterone secretion by Leydig cells only occurs when
stimulated by LH from the anterior pituitary gland and
 The rate of secretion is almost proportional and
 Anterior pituitary gland secretion of LH and FSH is inhibited
by testosterone-Negative feedback control
70
Role of FSH and Testosterone on Spermatogenesis
 Both FSH and testosterone are obviously necessary for
spermatogenesis
 FSH binds with specific FSH receptors at the Sertoli cells
 This causes the Sertoli cells to grow and secrete various
spermatogenic substances.
 Simultaneously, testosterone (and DHT) diffusing into the
seminiferous tubules also
 Cause strong tropic effect on spermatogenesis
71
Role of Inhibin in Negative Feedback Control
 This hormone has a strong direct effect on the anterior
pituitary gland to inhibit the secretion of FSH
 It operates with and in parallel of the negative feedback
mechanism for control of testosterone secretion
72
Human Chorionic Gonadotropin
 Secreted by the placenta and circulates both in the
maternal and fetal circulation
 Stimulates testosterone secretion by the fetal testes
 Has almost the same effects on the sexual organs as LH
73
Female Physiology Before
Pregnancy and Female Hormones
By; T/berhan H.
MSc in Medical Physiology
Composed of;
 Gonads;
◦ Ovaries
 Reproductive tract;
◦ Uterine (fallopian) tube
◦ Uterus
◦ Vagina
 External genitalia
◦ vulva;
 Vaginal opening
 Clitoris
 Labia minora/majora
 Accessory glands
◦ Vestibular glands
Functions;
◦ Production of ova (oogenesis)
◦ Reception of sperm from male
◦ Transport of ova
◦ Maintenance of developing fetus
◦ Childbirth (parturition)
75
Female reproductive system
Female reproductive system
Composed of;
• Gonads;
– Ovaries
• Reproductive tract;
– Uterine (fallopian) tube
– Uterus
– Vagina
• External genitalia
– vulva;
• Vaginal opening
• Clitoris
• Labia minora/majora
• Accessory glands
– Vestibular glands
Functions;
• Production of ova
(oogenesis)
• Reception of sperm and
fertilization
• Transport of ova
• Maintenance of developing
fetus
• Childbirth (parturition)
76
77
78
OOGENESIS AND FOLLICULAR
DEVELOPMENT
• Oogenesis; differentiation of developing egg
(oocyte) into a mature egg (ovum)
• Starts with migration of primordial germ cells
First from the dorsal endoderm of the yolk sac to
the outer surface of the ovary – with repeated cell
division
Then further into the substance of the ovarian
cortex - now called oogonia or primordial ova
79
….cont
• Then each oogonia collects spindle cells from the
ovarian stroma around it and
• These cells take on an epithelioid characteristics which
are then called granulosa cells.
• The ovum at this stage is now called primordial follicle
(primary oocyte)
• By the fifth month of fetal development, the oogonia
completes mitotic replication and prophase I
80
…cont
• From then, mitotic cell division ceases and no additional
oocytes are formed
• At birth there are about 1 to 2 million primary oocytes
At puberty
• Meiotic cell division of the oocyte continues and completes
meiosis I
• So, each oocyte divides and gives a large secondary oocyte
(ovum) and a small first polar body where both containing 23
pairs of chromosomes
81
….cont
• The first polar body disintegrates with/without second
meiotic division
• The ovum then starts second meiotic division, and paused
at metaphase II
• If fertilization occurs meiosis II will continue and
complete it’s stages
• Half of the sister chromatids remain in the fertilized ovum
and the other half are released in the second polar body
82
….cont
• At puberty, only a small percentage of the only
300,000 oocytes remained in the ovaries become
mature
• Out of these, only 400 to 500 of the primordial
follicles develop enough to expel their ova (one
each month) during reproductive life (13-46 years
of age)
• The remaining thousands of oocytes degenerate
83
84
FEMALE HORMONAL SYSTEM
Consists of three hierarchies of hormones
• Hypothalamic hormone - GnRH
• Anterior pituitary hormones – FSH and LH
• Ovarian hormones - estrogen and progesterone
Secretion;
• GnRH is secreted in short pulses once every 90 minutes like in males
• But the secretion rate of the other hormones during the monthly
sexual cycle is quite different
85
86
MONTHLY OVARIAN CYCLE;
• Average monthly sexual cycle is 28 days (20-45)
• Two importance;
1. Release of single ovum each month
2. Preparation uterine endometrium for implantation
The monthly ovarian changes are completely due to the
gonadotropic hormones, FSH and LH
In the absence of these hormones, the ovaries remain
inactive
Starts at puberty (age of 11-15 years) 87
1) FOLLICULAR PHASE OF THE OVARIAN
CYCLE
• At birth each ovum is surrounded by a single
layer of granulosa cells – which is called
primordial follicle
• Till puberty the granulosa cells;
1. Provide nourishment and
2. Secrete an oocyte maturation inhibiting factor
(that keeps them in prophase I)
88
• At puberty; higher amount of FSH and LH is
secreted
• The ovaries with some of the follicles within it
begin to grow
• The first stage of follicular growth begins with
Moderate enlargement of the ovum, (twofold to
threefold)
Growth of additional layers of granulosa cells
Which are now called primary follicles
89
Development of Antral and Vesicular Follicles
• FSH, cause accelerated growth of 6 - 12 primary
follicles each month
• Rapid proliferation of the granulosa cells, giving
rise to many more layers
• Then spindle cells (from the ovary interstitium)
collect around the granulosa cells, giving rise to
a second mass of cells called the theca
90
• Theca has two cell layers
1. Theca externa – is the outer layer
 Develops into a highly vascular connective tissue
capsule
 Becomes the capsule of the developing follicle
2. Theca interna – inner layer
 Develops an epithelioid nature like the granulosa
cells and
 Develop the ability of secreting additional steroid
sex hormones (estrogen and progesterone)
91
• After days of proliferative phase of growth,
granulosa cells secretes a follicular fluid that
contains a high concentration of estrogen
• As a result an antrum appears within the mass
of granulosa cells
• This whole growth of primary follicle up to the
antral stage is stimulated by FSH alone
92
• Then even larger follicles called vesicular follicles
develops more rapidly as a result of;
1. Increased number of FSH receptors formed by
granulosa cells due to the secretion of estrogen in to
the follicle. This makes the granulosa cells even more
sensitive to FSH – positive feedback
2. Both FSH and estrogen promote LH receptors on the
granulosa cells, allowing LH stimulation and creating
an even more rapid increase in follicular secretion.
3. The increased estrogen and LH act together to cause
proliferation of the follicular thecal cells and increase
their secretion as well.
93
• Then antral follicles begin to grow rapidly
• The ovum itself enlarges with about 3-4 fold in
diameter, resulting in total increase of up to
10-fold, or a mass increase of 1000-fold.
• As the follicle gets enlarged, the ovum is kept
at one pole of the follicle surrounded in a mass
of granulosa cells.
94
• Only one follicle fully matures each month
– Outgrowth of one follicle and atresia of the other all (5 - 11
developing follicles), and the probable reason is
– The negative feedback of estrogen from the most rapidly growing
follicle causing on hypothalamus, where
– The largest follicle continues to grow due to its intrinsic positive
feedback effects
– This is important because it prevents development of more than
one child in each pregnancy
– At ovulation, only a single follicle matures with a diameter of 1 -
1.5 cm & called the mature follicle
95
96
Ovulation
• Through the process of rapid follicular development a
protruding outer wall of the follicle begins to swell like a nipple
called stigma
• Then, fluid begins to ooze from the follicle through the stigma,
that later ruptures widely and allowing a more viscous fluid,
which has occupied the central portion of the follicle, to
evaginate outward.
• This fluid carries with it the ovum surrounded by corona radiata
(mass of several small granulosa cells).
• Ovulation occurs 14 days after the onset of menstruation in a woman
with 28-days of female sexual cycle.
97
A surge of LH is needed for ovulation
• 2 days prior to ovulation, LH secretion rises 6 - 10 fold &
peaks about 16 hours before ovulation
• Similarly FSH increases 2-3 fold and
• Both FSH and LH act synergistically to cause rapid swelling
just a few days before ovulation.
• The LH also causes the granulosa and theca cells mainly
secrete progesterone
• As a result rate of estrogen secretion falls about 1 day before
ovulation
98
Initiation of ovulation
• LH causes the rapid secretion of follicular steroid hormones
mainly containing progesterone
• This in turn causes two main events to happen which are
important for ovulation:
1. Release proteolytic enzymes from lysosomes by theca externa
 Causing degeneration and weakening of the stigma wall and
 Further swelling of the entire follicle
2. Rapid growth of new blood vessels into the follicle wall, and
secretion of prostaglandins (local vasodilators)
• As a result of these two events there will be transudation of
plasma into the follicle that furthers add to the swelling
• Finally, the follicular swelling & degeneration of the stigma
causes rupture of the follicle and discharge of the ovum.
99
100
2) LUTEAL PHASE OF THE OVARIAN
CYCLE
• After a few hours of ovum expulsion, the remaining granulosa
and theca interna cells change rapidly into lutein cells
• These cells enlarge in diameter (>2x) and become filled with
lipid inclusions that give them a yellowish appearance
• This process is called luteinization, and the total mass of cells
together is called the corpus luteum
• A well-developed vascular supply also grows into the corpus
luteum
101
• The granulosa cells in the corpus luteum form
large amounts of the female sex hormones
progesterone and estrogen (more progesterone
than estrogen) and
• The theca cells form mainly androgens
(androstenedione and testosterone)
• However, most of these hormones are converted
into estrogens by the aromatase enzyme in the
granulosa cells
102
• The corpus luteum will have about 1.5 cm of
diameter after 7 - 8 days of ovulation.
• Afterwards it begins involute and eventually
loses its
– Secretory function
– Yellowish and lipid characteristic and
– Becomes the corpus albicans that is replaced by
connective tissue which is finally absorbed
103
Luteinizing Function of LH ;
• LH is responsible for the conversion of granulosa
and theca interna cells into lutein cells
• This function gives LH its name - “luteinizing,”
for “yellowing”
• Until ovulation local hormone in the follicular
fluid, called luteinization-inhibiting factor, hold
the luteinization process in check
104
Secretion by the Corpus Luteum (role of LH):
• Corpus luteum is a highly secretory organ, that continues to
secrete large amounts of progesterone and estrogen
• Once LH (mainly secreted during the ovulatory surge) has acted
on the granulosa and theca cells,
• The newly formed lutein cells seem to be programmed to go
through predetermined sequence of
1. Proliferation
2. Enlargement, and
3. Secretion, followed by
4. Degeneration
• All this occurs in about 12 days.
105
Involution of Corpus Luteum and onset of next ovarian cycle
1. Estrogen in particular and progesterone to a lesser
extent, have strong feedback effects in maintaining low
levels of FSH and LH
2. Similarly inhibin hormone secreted by lutein cells also
inhibits FSH secretion
• Both thess causes low secretory rates of FSH and LH
• Low or total loss of FSH and LH finally causes the corpus
luteum to degenerate completely
• This process called involution of the corpus luteum.
106
• This happens at the end of 12th
day of corpus luteum
life (26th
day of the sexual cycle) which is 2 days
before menstruation begins.
• The sudden cessation of estrogen, progesterone, and
inhibin secretion by the corpus luteum removes the
feedback inhibition of the anterior pituitary gland,
• This results in the secretion increased amounts of
FSH and LH again and
• Beginning of new ovarian cycle
107
Monthly Uterine Cycle
• Refers to cyclical changes in the endometrial lining of the uterus
• Resulting in an overt bleeding from the genital tract
• Also called endometrial cycle
• Is the period between menstrual flows
• Involves cyclic rise and fall in female reproductive hormones
• Is variable at the extremes of reproductive ages
Rationale
• Periodic preparation for fertilization + pregnancy
108
A. Proliferative Phase (Estrogen phase)
 Begins with the last days of menses and ends around ovulation
 Dominant ovarian hormone: estrogen
Main events;
a. Stroma & epithelium:
•↑ Proliferation and growth of epithelial + stromal cells.
•At the time of ovulation the endometrium regains its thickness (3 - 5 mm thick)
b. Glands:
• Progressive growth of endometrial glands
• Cervical epithelium secrets a thin, watery mucus
c. Angiogenesis:
• Lengthening of the vessels
• Neovascularization of layers
d. Receptors:
• ↑Estrogen + progesterone receptors on endometrial cells
109
110
Uterine gland
Uterine artery
Uterine lumen
Organization of glands and blood flow within the uterine endometrium
B. Secretory Phase (Progestational Phase)
a. Duration: 14th
- 28th
day.
b. Predominant hormone:
• Progesterone (10x, corpus luteum).
• Estrogen
c. Epithelium and stroma:
• Marked secretory changes and swelling of the endometrium
• Further thickening of endometrium
• All these changes are important for implantation of fertilized ovum
• ↑ Adhesivity of surface epithelium.
d. Mucous glands:
• Elongation and coiling
• Secrete thick viscous fluid
• Glycogen
• Cervical mucus becomes thick
f. Angiogenesis:
`
• Spiraling of the blood vessels
• ↑ Vascularity
g. Receptors:
• ↓ Number of estrogen + progesterone receptors.
111
Organization of glands and blood flow within the uterine endometrium
112
C. Menstrual Phase
I. If no fertilization + no production of hCG, CL involutes →↓E, P
(Luteolysis/luteal regression).
Then 3 events follows to cause menstrual bleeding
a. ↓ E, P → ↓ stimulation of endometrial cells → rapid involution
of the endometrium → ↑ local Pgs
b. Then, vasospasm of the tortuous blood vessels (due to Pgs) →
↓nutrients → ischemia and necrosis → formation of hemorhagic
and edematous layer, then
c. Desquamation and separation of the necrotic outer layer →
initiation of uterine contractions that expel the uterine contents
→ bleeding
II. If conception occurs: the functional life span of corpus luteum is
extended (due to hCG)
113
114
115
Normal menstrual cycle:
a. Duration: 2-8 d
b. Cycle length: 21-35 d (28 + 7)
c. Vol. blood loss: 20-150ml (aver. 50ml).
d. Type of blood flow: 75% arterial, 25% venous.
e. Contents: tissue debris, Pgs, fibrinolysin
f. No clot formation:
but, (if no fibrinolysin + excessive bleeding → clot formation)
116
Cervical Cycle
Quantity + quality of mucus is changed
i. E: → Profuse, watery, alkaline (penetrability by sperm is maximal)
ii. P: scanty, viscous, infiltration with cellular elements
Vaginal cycle
i. E: ↑Cornification (hardening), ↑ acidophilic cells (Pap smear)
ii. P: Thick mucus, infiltration with PMNL, ↓acidophilic cells
117
Cyclic Changes in the Breasts
• E: Proliferation of mammary ducts.
• P: causes growth of lobules and alveoli.
• Distention of ducts/hyperemia + edema → breast swelling,
tenderness & pain.
118
The cycle of ovulation and menstruation
119
Physiological and behavioral variables
1. Core body temperature
• 0.5°C in the luteal phase/oral or rectal.
• Progesterone/resetting thermostat center + thermogenic effect.
2. Sensory acuity
• Olfactory acuity (menstrual synchronization).
3. Sexual activity
• Human female sexual behavior around the mid-cycle
( Androgens)
4. Eating behavior and body weight
•  Food intake in luteal phase ( 5-HT activity).
120
Hypothalamic – Hypophyseal - Ovarian Axis
Purpose
a. Production of physiologic quantities of sex steroids
b. Generation of healthy ova that become mature female gamets
121
Components
a. Hypothalamic GnRH/LHRH Hypophysis
Neural
b. Hypophyseal Gns Ovary
LH, FSH
c. Ovary
i. Granulosa cells Estradiol/inhibin/activin
ii. Thecal cells Androgens/estradiol
 Negative feedback
 Positive feedback control
122
Negative Feedback
123
Positive Feedback Negative Feedback
?
?
124
Hypothalamus
GnRH
Gonadotropes
LH FSH
Theca cells Granulosa cells
Androgens
Inhibin
+
¯
+ +
+
Estradiol
¯
¯
Chronic illness
Weight & fat loss
Stress, drugs, exercise
¯
GnRH analogues
• Breast Ca.
• Endometriosis
• Leiomyomas
Summary of H-P-O axis
The Physiology of Ovarian Hormones
1) Estrogens (17β-estradiol, estrone, estriol)
a. Biosynthesis;
Origin: Ovary: granulosa cells + theca cells
Corpus Luteum
Placenta/pregnancy
Adrenal cortex
Testis (Males: Sertoli cells, aromatization)
Chemistry
Precursors: Cholesterol/C-27 Animal fat in the diet,
De Novo synthesis.
125
b. Secretion and bioavailability;
•98% is found bound to carrier proteins.
38% to sex hormone binding globulin (SHBG)
60% to plasma albumin
•2% exist in free form.
c. Metabolism:
Liver → bile, urine
126
2) Progestins: Progesterone
17α-hydroxyprogesterone
Origin: Ovarian follicles
Corpus luteum
Placenta/pregnancy
Adrenal cortex
Testes/males
127
Synthesis
• Cholesterol (C-27) → C-21 steroid
Bioavailability
•Bound to: 80% to albumin
18% transcortin (CBG)
2% Free
Metabolism: Liver (urine)
128
The Physiological adjustments to Pregnancy
a. Amenorrhea
b. Morning sickness
•4th
-5th
week of pregnancy/peak at the 8th
week.
• Disappears at 14th
week.
•??? hCG
•??? Steroids of pregnancy→↓ Intestinal motility
129
130
c. Enlargement of reproductive tract
•Ovary: ↑ size/∵ CL of pregnancy.
•Uterus: 50gm → 1100gm (volume = stretching + hypertrophy).
• Cervix: ↑
• Vagina + vulva: ↑
•Breasts: ↑ (2x)
d. Acromegalic features
e. Weight gain:  11-12.5kgs
oFetus = 3.5kgs
oAmniotic fluid, placenta + fetal membranes = 2kgs
oUterus = 1kg
oBreasts = 1kg
oBlood & ECF = 2.5kg
oFat = 1 kg
131
• ↑Appetite + food intake/hormonal + flow of substrates from the maternal
blood to the fetus
f. BMR: ↑10-15% (↑T4
, ↑sex steroids, ↑adrenocortical hormone).
(To supply energy that is expended to carry the extra load.)
g. Hematological changes:
•  Blood volume: 40-45% (Plasma volume +RBC mass/450ml, plasma>RBC)
• ↑Plasma volume → haemodilution → Physiological anaemia
(↓ RBC count, ↓ Hb, ↓ Hct).
• ESR (plasma globulins, fibrinogen).
•  Fe requirement
Significance of volume expansion:
• It meets the metabolic demands of the enlarged uterus and its greatly
hypertrophied vascular system.
• It provides abundant nutrients and elements to support the rapidly
growing placenta and fetus.
• It protects the mother, and in turn the fetus, against the deleterious
effects of impaired venous return in erect positions.
• It safeguards the mother against the adverse effects of parturition-
associated blood loss.
132
Δs in total blood volume + plasma + RBC volumes during pregnancy
133
134
h. Cardiovascular
• ↑ CO (35%, 27wks) → ↑ HR, ↑SV (Placenta: A-V shunt).
• ↑ Venous return
• ↑ Blood flow: lungs, skin, kidneys, GIT, coronaries and breasts).
• ↑ Blood volume: 1-1.5l
• ↑ Uteroplacental blood flow: uterus, placenta/625ml/min.
I. Renal
• ↑ GFR/50% → ↑ Urine output
i. Hypervolemia-induced haemodilution lowers the protein
concentration and oncotic pressure of plasma entering the
glomerular microcirculation.
ii. Renal plasma flow increases by approximately 80%
• Gravid uterus compresses the bladder + ↓volume capacity →
↑frequency of urination
135
136
Cardiovascular and renal changes in pregnancy
J. Respiration
• ↑ O2
requirements (30%).
• ↑ Minute ventilatory volume/↑30-50%
i. To supply the fetus + to support the increased metabolic rate.
ii. Progesterone increases sensitivity of respiratory chemoreceptors
to CO2
+ ventilation is adjusted to keep the arterial PCO2
lower
than normal.
• ↑ Tidal volume, inspiratory capacity
•  Peak expiratory flow rate
137
• Airway conductance, Total pulmonary resistance.
• ↓ Functional residual capacity (↓Expiratory reserve +↓Residual volume).
• ↓ Total lung volume, ↓ Inspiratory reserve.
• Total lung capacity remains unchanged.
• Expanding uterus pushes the abdominal viscera up against diaphragm
and interferes with breathing/↑RR.
138
k. Immune system
• Cell-mediated immunity is suppressed
(Maintenance of pregnancy + protection of the fetus, progesterone).
l. GIT
• ↑ Gastric emptying time, ↓ intestinal motility → constipation
(↑ Progesterone).
• ↓ lower esophageal sphincter tone → reflux esophagitis or
‘Heartburn’ (↑ Progesterone).
139
140
m. Integumentary system
I. Hyperpigmentation (   MSH).
• ↑ Melanocyte activity:
Darkening of the areola.
Linea nigra (mid line below umbilicus)
• Temporary darkening of the skin (nose, cheeks – ‘Mask of
pregnancy’, chloasma).
 ↑ Gravid uterus→ stretching the dermis-tears the collagen tissue →
striae gravidarum/reddish → silver white/
II. Vascular changes (hyperestrogenemia).
• Angiomas/spider angiomas (face, neck, upper chest, and arms).
• Palmar erythema
141
n. Endocrine system
i.Anterior pituitary
• ↑ 50% increment in size, ↑ TSH, ↑ Prolactin.
• ↓ FSH, LH/∵ inhibitory effect of E + P from the placenta.
• ↓ GH
ii. Adrenal cortex
• ↑Plasma glucocorticoids
• ↑ Aldosterone/2x → ↑ salt + H2
O retention/hypertension.
142
iii. Thyroid Gland (↑50%)
• ↑TSH → ↑ T3
, T4
→ ↑ BMR
iv. Parathtyroid Glands
• ↑ Size → ↑ PTH → mobilize Ca2+
from the mother’s bone to make
it available to the fetus
143
v. Relaxin (Corpus Luteum & placenta)
a.Remodeling of the pelvic girdle, softening of the Cx + the
vagina
b.Cervical softening, effacement + dilatation, decrease time to
delivery
c.Laxity of pelvic joints and separation of the pubic symphysis
d.Relaxin + Progesterone → inhibit myometrial contractions →
quiescence → maintenance of pregnancy
The Endocrine Placenta
Placental Functions: Respiratory, Nutritive, Excretory, Endocrine
o Maintains a quiescent gravid uterus
o Maternal physiology to ensure fetal nutrition in utero.
o Maternal pituitary function + mammary gland development
o Determines the time of labor and delivery.
o Source of hCG
144
145
Role of the placenta in exchanges between the fetal & maternal compartments
146
Peptide hormones: hCG + hPL
Others: Relaxin, inhibin, GnRH, ACTH, CRH, TRH, IGFs
β-endorphin,
147
Human chorionic gonadotropin (hCG)
• Origin: syncytiotrophoblast of the placenta.
• Synthesis: glycoprotein, 236aa, 38kd, 2 noncovalently linked
subunit (α, β)
• Homology: LH, FSH, TSH
(Luteinizing + Luteotropic).
• Secretion and plasma
o 6-8d after conception
o Peak: 60-90d
o Plateauing: 120d before delivery.
o After delivery: 12-24hrs.
o ↑ hCG: Multiple pregnancy
Rh – isoimmunization
Diabetic woman in pregnancy
Choriocarcinoma
o  hCG: Ectopic pregnancy
Miscarriage ….???abortion
148
149
• Function:
a. Maintain the early corpus luteum of pregnancy (LH).
b. Promote steroidogenesis.
c. Regulate the development + secretion of T by the fetal testes
d. Give immunological privilege to the developing trophoblast.
150
Circulating levels of hCG in maternal blood during pregnancy.
151
Human Placental Lactogen (hPL, CGP, hCS)
•Origin: syncytiotrophoblast
•Chemistry: a single chain polypeptide
•Homology: GH
•Secretion & Plasma
o 3rd
week after conception.
o Appears at plateau at term.
o [hPL]  placental weight.
•Nature
o Mainly - lactogenic activity
o 3% - growth promoting activity
o t½ = 20min (it can not be detected after birth).
152
• Functions
a. Spares maternal glucose → providing continued nutrition for the
developing fetus (insulin-resistance state).
b. hPL exerts metabolic effects in pregnancy similarly to those of GH.
i. Stimulation of lipolysis → ↑ free FA (accelerated starvation).
ii. Inhibition of glucose uptake in the mother → development of
maternal insulin resistance (diabetogenic).
iii. Inhibition of gluconeogenesis →↑ transportation of glucose and
protein to the fetus.
Placental Steroid Hormones
1. Progesterone
•Source and synthesis: maternal cholestrol, trophoblast
•Functions:
a.Progesterone binds to receptors in uterine smooth muscle
→↓RMP
→ inhibiting smooth muscle contractility →myometrial quiescence
→ prevents premature expulsion of fetus
b. Secretory endometrium → decidua/histiotropic + hemotropic nutrition.
c. Inhibits Pgs formation and other paracrine factors
d. Maintenance of pregnancy: inhibit T-lymphocyte cell-mediated
response
e. Breasts: lobuloalveolar development.
153
154
Maternal serum level of progesterone during pregnancy
155
2. Estrogen
•Origin: Corpus luteum (early wks of preg.) +
syncytiotrophoblast
•Urinary estriol excretion of the mother → index of the state of
the fetus
•It should be steadily increasing throughout pregnancy if the
fetus is growing normally
Functions:
a. Stimulate Pg synthesis
•↑ Uterine blood flow (↑fetal organ maturation + development)
b. Mediate the growth + development of the maternal reproductive
organs
c. Stimulates phospholipid synthesis + turnover
156
Maternal serum levels of estrogens during pregnancy
157
Secretion rates of placental hormones
The Physiology of Parturition
1. Defiition  delivery of the baby
•Duration of gestation; 40wks
2. Mechanisms: not known completely
 Mechanical factors
a.Distension of uterus (fetal age size) → ↑ stretching of
smooth muscle, inherent rhythmicity) → ↑ contractility.
158
b. Uterine contractions (Braxton Hicks contractions +ve feedback)
↑ Distension + effect of hormones
↓
Uterine contractions
↓
The increased pressure of the baby’s head against the cervix with each
contractions excites the fundus or body of the cervix to contract
↓
Dilatation of cervix & distension of vagina.
↓
Stimuli from the cervix + vagina
↓
↑ Secretion of oxytocin
↓
↑ Uterine contraction until they are strong enough to expel the baby
159
 Neuroendocrine factors
a. Progesterone withdrawal
•↓ P at the end of gestation period →↓No. of myometrial
progesterone receptors
•↓ Antagonistic effect of progesterone to oxytocin + Pgs
•↓ Progesterone → synchronizing uterine contractions
160
161
b. Estrogen
•↑ E (in amount) →↑ prostaglandin synthase activity in the
tissues
of the uterus + fetal membrane →↑ myometrial contractions.
•↑ E →↑ myometrial + endometrial oxytocin receptors.
•↑ E →↑ oxytocin production & secretion by the
neurohypophysis
c. Oxytocin
•↑ Uterine contractions/distension + E.
•↑ Oxytocin →↑Pg → stimulate uterine smooth muscle
contraction → expulsion of the fetus
162
d. Relaxin
•Relaxes the pubic ligaments + relaxes the lower part of the uterus.
•Ripen/soften cervix → so eases the passage of the offspring at
birth.
•↑ Sensitivity of the uterus to oxytocin.
e. Prostaglandins
•↑ E →↑Pg synthesis →↑ Intracellular Ca2+
in the myometrium
→ uterine contractions
•Act synergistically with oxytocin/cervical ripening, softening,
dilatation, contractions
3. Mechanics of Labor
a.Uterine contractions begins at the fundus + spread downward
over
the body of the uterus
b. Intensity of contraction is stronger at the fundus than in the lower
segment of the uterus - force the baby downward toward the cervix
c. Frequency of contractions: onset: once in every 30min
later: once in 1 to 3 min.
 Intermittent contraction will not stop the blood flow thru the placenta and
the fetus will not die.
163
164
d. Stages
• 1st
stage: the period from onset of labor up full cervical
dilatation - (8-24hrs or less)
• 2nd
stage: the time interval from the full dilatation of the cervix
till delivery of fetus (hrs to minutes)
• 3rd
stage: the time taken for separation and delivery of the
placenta (10-45min)
• Duration of each stage tends to be longer in a primipara than in a
multipara
The Mammary Glands and Lactation
• Mammary glands: replaces the nourishing function of the placenta
after birth.
• Lactation → evolutionarily conserved mammalian physiological
function.
1. Mammogenesis
• Puberty: ↑ Estrogen → duct growth
↑ Progesterone→ lobuloalveolar growth
Permissive role: GH + glucocorticoids + PRL + Insulin.
• Pregnancy: milk secretion doesn’t occur (Inhibition of placental E + P)
Following delivery placental E+P ↓→ lactation begins
165
166
2. Lactation
a. Milk synthesis: initiated during the end of pregnancy/PRL, hPL
b. Lactogenesis: synthesis of milk by alveolar cells & its secretion is
initiated by the loss of placental steroids after birth.
c. Galactopoiesis: maintenance of established lactation, controlled by
PRL
d. Milk ejection: passage of milk from alveolar lumen to the duct system
and collection in the ampulla and larger ducts
delivery to the infant
• Controlled by oxytocin.
Relationship of the alveolar lobules and duct system
Arrangement of alveoli in a mammary lobule.
167
3. Milk Ejection Reflex
Nipples (Mechanoreceptors → suckling)
↓
Somatic touch pathways (multisynaptic pathway) induced
↓
Signals sent to Hypothalamic nuclei (SON, PVN)
↓
Oxytocin neurons release oxytocin
↓
Induces contraction of myoepithelial cells that surround alveoli and ducts
↓
Mobilization of milk from the alveoli and duct system
to the nipple
↓
Producing the sensation of ‘milk let-down’ in the mother.
168
3.12.3. Milk Secretion Reflex
Suckling of nipples (mechanoreceptors)
↓
Somatic touch pathways (multisynaptic pathway)
↓
Hypothalamic nuclei
↓
Inhibition of PIH secretion
↓
Secretion of PRL from the anterior pituitary
↓
Stimulation of milk secretion by the mammary glands
169
Suckling reflexes
170
171
4. Components of milk
• Protein: casein, α-lactalbumin, β-lactoglobulin
• CHO: lactose, fat, minerals (Ca, Mg, P, Fe).
• Electrolytes: Cl-
, K+
, Na+
…
• Vitamins
• Immunoglobulins: IgMs, IgEs, IgAs
• Growth factors: EGF, IGF-1…
172
5. Lactation and Menstrual Cycle
• Mothers who do not nurse → menses/6 wks after delivery.
• Regular nursing→ amenorrhoeic/25-30wks.
• 50% of the cycles in the first 6 months → anovulatory
6. Lactation as a Contraceptive
a. Suckling →↑ PRL secretion → inhibits GnRH/LHRH secretion.
b. Inhibits the action of GnRH on gonadotropes
c. Antagonizes the action of gns in the ovaries.
FEMALE SEXUAL ACT
• Sexual desire is higher during ovulation (may be
due to higher estrogen)
• Like in males effective sexual act depends on both
psychic stimulation and local sexual stimulation
• Local sexual stimulation includes
– Clitoris
– Vulva, vagina, and other perineal regions
173
• Sexual sensory signals pudendal nerve
and sacral plexus sacral segments of the
spinal cord cerebrum
• But local integration reflexes in the sacral and
lumbar spinal cord are also responsible for
some of the reactions
174
Female Erection and Lubrication
• Controlled by parasympathetic NS
• Identical erectile tissues with the glans penis
extends from introitus up to the clitoris
undergoes similar events like in males
• Vasodilation and accumulation of blood on
these areas tightening of introitus
175
• Parasympathetic NS also also the bilateral
Bartholin glands mucus secretion inside
the introitus
• Much lubrication is also provided by mucus
secreted by the vaginal epithelium
176
Female Orgasm
• Also called female climax
• Best achieved from both sexual stimulations
• Is analogous to emission and ejaculation in male
• Promote fertilization of ovum
• Resolution – after sometime of the orgasm
177

Reproductive system Physiology powerpoint.pptx

  • 1.
    Reproductive Physiology By; T/berhanH. MSc. Medical Physiology
  • 2.
    2  Process of; ◦Procreation: maintenance of ones species ◦ Recreational and Relational  Two types of reproduction 1. Asexual; Binary fission, budding, ..... 2. Sexual; involves copulation of male and a female of the same species Reproduction
  • 3.
    3  Sexual reproductionresults in genetic diversity due to  Shuffling of genes  Crossing-over in meiosis and  Fertilization  Sexual reproduction produces new individual that is genetically different from it’s parents  So new combinations of genes occur in each generation. ….cont
  • 4.
    4  During 7th weekof IUL, bi-potential primordial germ cells (primitive gonadal cells) appears  The embryo has a primitive female and male genital tracts called the Mullerian and Wolffian duct respectively.  In the absence of Y-chromosome, these germ cells develop into ovaries  In the presence of Y-chromosome, the primitive gonadal cells develop into testis Development and differentiation of reproductive organs and tracts
  • 5.
    5  In theabsence of functioning testis ◦ The Wolffian duct regresses and ◦ The Mullerian duct develops into the female internal genitalia; the fallopian tube, uterus and upper 2/3 of vagina ◦ The urogenital slit remains open and the female external genitalia develops.  In the presence of functioning testis ◦ Wolffian duct develops into the male internal genitalia, ie, epididymis, vas deferens, seminal vesicles and prostate ◦ Urogenital slit is closed and male external genitalia (penis and scrotum) develops
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    Composed of;  Gonads; ◦Testes  Reproductive tract; ◦ Epididymis ◦ Vas deference ◦ Urethra  External genitalia ◦ Penis;  Corpora cavernosa  Corpora spongiousum  Accessory glands ◦ Prostate ◦ Seminal vessicles ◦ Bulbourethral glands Functions; ◦ Production of sperm (spermatogenesis) ◦ Delivery of sperm to female 9 Male reproductive system
  • 10.
    10 Seminiferous tubule  Thereare about 900 coiled seminiferous tubules in both testis  Each averaging more than one-half meter  Site of sperm production Epididymis  Coiled tube which is about 6 meters long  The next structure where sperm is emptied and  Site of sperm storage
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    Male reproductive functionscan be divided into three major subdivisions: 1. Spermatogenesis - formation of sperm cells 2. Performance of the male sexual act 3. Production of hormones 12
  • 13.
    At embryonic life, Primordial germ cells migrate into the testes and  Become immature germ cells called spermatogonia, which  Lie in inner surfaces of the seminiferous tubules During puberty,  Spermatogonia begin to undergo mitotic division and continually proliferate and differentiate to form sperm  It begins at an average of 13 years of age and  Continues throughout life  But decreases markedly in old age  It happens as a result of stimulation by gonadotropic hormones from anterior pituitary 13 SPERMATOGENESIS
  • 14.
     Serious ofrepeated mitotic cell division happens first  During these cell divisions spermatogonia migrate toward the central lumen of the seminiferous tubule along with Sertoli cells and mature to become primary spermatocytes 14 STEPS OF SPERMATOGENESIS
  • 15.
     Then twosuccessive meiotic division happens  Which are Meiosis I (secondary spermatocyte) and Meiosis II (spermatids)  Spermatids are progressively modified to become spermatozoa (sperm)  Each spermatids finally have haploid (23) chromosomes due to the meiotic division  The whole process takes about 74 days 15 ….cont
  • 16.
     Among the23 pairs of chromosomes in each spermatogonium, one pair is composed of sex chromosomes (X and Y chromosomes)  During meiotic division each strand of the sex chromosome goes to one spermatid  This determine the sex of the eventual offspring 16
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    Testosterone;  Secreted bythe Leydig cells  Essential for growth and division of the testicular germinal cells - the first stage of sperm cell formation Luteinizing hormone;  Secreted by the anterior pituitary gland  Stimulates the Leydig cells to secrete testosterone 19 Hormones that stimulate Spermatogenesis
  • 20.
    Follicle-stimulating hormone;  Anotherhormone from anterior pituitary gland,  Stimulates the Sertoli cells Estrogens;  Formed from testosterone by the Sertoli cells when stimulated by FSH  Believed to be essential for spermiogenesis 20
  • 21.
    Growth hormone ; Important in controlling metabolic functions of the testes, as well as  It promotes early division of the spermatogonia  In its absence, spermatogenesis is severely deficient or absent, thus causing infertility. 21
  • 22.
     Sperm cellremoved from the seminiferous tubules and/or early portions of the epididymis are non- motile and cannot fertilize an ovum.  In the epididymis sperm cells continue to undergo some developmental stages and continue to get matured, but  Still several inhibitory proteins in the epididymal fluid prevent final motility until after ejaculation. 22 Maturation of Sperm in the Epididymis
  • 23.
     Before ejaculation,sperm cells are not motile and can’t fertilize an ovum  Full motility is achieved after ejaculation  Ejaculated sperm cells also have special nutrient fluid (from Sertoli cells and the epithelium of the epididymis)  This fluid contains hormones (like testosterone and estrogens), enzymes, and special nutrients that are essential for sperm nutrition 23
  • 24.
     Each dayabout 120 million sperm cells are produced on both tests.  Majority of these sperm are stored in the epididymis, but  Small quantity is stored in the vas deferens  Can be stored maintaining their fertility for at least a month  During this stay, these are kept in a deeply suppressed, inactive state by multiple inhibitory substances 24 Storage of Sperm in the Testes
  • 25.
     Matured fertilesperm can move on fluid medium at velocities of 1 to 4 mm/min.  The activity of sperm is greatly enhanced in a neutral and slightly alkaline medium  But, it is greatly depressed in a mildly acidic medium.  Strong acidic medium can cause the rapid death of sperm. 25 Physiology of the Mature Sperm
  • 26.
     Increasing temperatureincreases the activity of sperm but so does the rate of metabolism,  But in such conditions the life span of the sperm cells is shorter and  Ejaculated sperm in the female genital tract can stay only for 1 to 2 days. 26
  • 27.
     Matured spermhave head and tail Head  The head contains thin cytoplasmic and cell membrane layer and mainly condensed with nucleus of the cell  The head on it’s outside anterior 2/3 is covered with a thick cup called acrosome, which is formed from Golgi apparatus 27
  • 28.
     The acrosomecontains two main enzymes  Hyaluronidase enzyme; which can digest proteoglycan filaments of tissues and  Powerful proteolytic enzymes; which can digest proteins  These enzymes play important roles in allowing the sperm to enter the ovum and fertilize it 28
  • 29.
    Tail(flagellum)  Is theother part of matured spermatozoa which has three major components: 1. A central skeleton constructed of 11 microtubules, collectively called the axoneme (similar to that of cilia) 2. A thin cell membrane covering the axoneme 3. A collection of mitochondria around the axoneme in the proximal portion of the tail (body of the tail). 29
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    Motility of sperm Achieved by the back-and-forth movement of the tail which results from a rhythmical longitudinal sliding motion of the anterior and posterior tubules of the axoneme.  This process gets it’s energy from ATP, which is synthesized by the mitochondria  Normal sperm move in a fluid medium at a velocity of 1-4 mm/min. 31
  • 32.
     Seminal vesiclesis lined with a secretory epithelium that ◦ Secretes a mucoid material ◦ With high amount of fructose, citric acid, and other nutrient substances ◦ It also contains large quantities of prostaglandins and fibrinogen  Seminal vesicle empties its contents into the ejaculatory duct which adds greatly to the bulk of the ejaculated semen, and  So the fructose and other substances in the seminal fluid are used as a source of nutrient for the ejaculated sperm 32 FUNCTION OF THE SEMINAL VESICLES
  • 33.
     Prostaglandins aidfertilization in two ways: 1. It reacts with the female cervical mucus and make it more receptive to sperm movement 2. It causes backward, reverse peristaltic contractions in the uterus and fallopian tubes and this help move the ejaculated sperm toward the ovaries 33
  • 34.
     Prostate glandsecretes a thin, milky fluid that ◦ Contains calcium, citrate ion, phosphate ion, a clotting enzyme, and a profibrinolysin. ◦ Is slightly alkaline that helps to neutralize the seminal fluids from the  Vas deference (due to the presence of citric acid and metabolic end products) and  Vaginal secretions (pH of 3.5 to 4.0).  Sperm cell become optimally motile and can fertilize the ovum at pH of 6.0 - 6.5.  So the slightly alkaline prostatic fluid helps neutralize the acidity of the other fluids and enhance the motility and fertility of the sperm.  The average pH of the combined semen is about 7.5, (more than neutralized by prostatic fluid) 34 FUNCTION OF THE PROSTATE GLAND
  • 35.
     Semen isthe fluid ejaculated during the male sexual act, which is composed of ◦ Fluid and sperm from the vas deferens (10%), ◦ Fluid from the seminal vesicles (60%), ◦ Fluid from the prostate gland (30%), and ◦ Small amounts from the mucous glands, especially the bulbourethral glands.  The bulk of the semen is seminal vesicle fluid, which is the last to be ejaculated and serves to wash the sperm through the ejaculatory duct and urethra. 35 SEMEN
  • 36.
    Semen has;  Milkyappearance – due to prostatic fluid  Mucoid consistency – due to fluid from the seminal vesicles and mucous glands  Sticky nature - due to clotting enzymes from the prostatic fluid that cause the fibrinogen of the seminal vesicle fluid to form a weak fibrin coagulum that holds the semen in the deeper regions of the vagina  The coagulum then dissolves during the next 15 to 30 minutes because of lysis by fibrinolysin formed from the prostatic profibrinolysin.  In the early minutes after ejaculation, the sperm remain relatively immobile, possibly because of the viscosity of the coagulum.  As the coagulum dissolves, the sperm simultaneously become highly motile 36
  • 37.
    Life span ofsperm;  For weeks in the male genital ducts  For only 24 to 48 hours at body temperature  For several weeks at lowered temperatures, and  For years when frozen at temperatures below −100°C 37
  • 38.
     Sperm cellcan’t fertilize an ovum immediately after ejaculation b/se the inhibitory factors are still present with the ejaculated semen  It needs further changes – “capacitation”  The basic changes are; 1. The uterine and fallopian tube fluids wash away the various inhibitory factors that suppress the sperm 2. Sperm swim away from the cholesterol vesicles that it covers towards the uterine cavity so that the membrane at the head of the sperm (the acrosome) becomes much weaker and allowing release of it’s enzymes 38 “Capacitation” of Spermatozoa
  • 39.
    3. The membraneof the sperm also becomes much more permeable to calcium ions, so  Calcium now enters the sperm in abundance and changes the activity of the flagellum, giving it a powerful whiplash motion in contrast to its previously weak undulating motion.  In addition, the calcium ions cause changes in the cellular membrane that cover the leading edge of the acrosome, making it possible for the acrosome to release its enzymes rapidly and easily as the sperm penetrates the granulosa cell mass surrounding the ovum, and even more so as it attempts to penetrate the zona pellucida of the ovum. 39
  • 40.
     Acrosome ofthe sperm contains large quantities of hyaluronidase and proteolytic enzymes. Hyaluronidase;  Depolymerizes the hyaluronic acid polymers in the intercellular cement  Open pathways between the granulosa cells so that the sperm can reach the zona pellucida. The proteolytic enzymes;  Digest proteins in the structural elements of tissue cells that still adhere to the ovum.  Open a penetrating pathway for passage of the sperm head through the zona pellucida to the inside of the ovum 40 “Acrosome Reaction” and Penetration of the Ovum
  • 41.
     After afew minutes of the first sperm penetrates the zona pellucida, calcium ions diffuse inward through the oocyte membrane and cause multiple cortical granules to be released by exocytosis from the oocyte into the perivitelline space.  These granules contain substances that permeate all portions of the zona pellucida and prevent binding of additional sperm, and they even cause any sperm that have already begun to bind to fall off.  Thus, almost never does more than one sperm enter the oocyte during fertilization. 41 Why does only one sperm enter the Oocyte?
  • 42.
    Two important areasof initiation 1. Glans penis; most important source of sensory nerve signals for initiating the male sexual act  The glans contains an especially sensitive sensory end- organ system that transmits into the central nervous system  Sexual signals from sensory end-organ pudendal nerve sacral plexus sacral portion of spinal cord undefined areas of the brain 42 MALE SEXUALACT
  • 43.
    Signals could alsocome from;  Outer nearby structures like the anal epithelium, the scrotum, and perineal structures  Internal structures, like in the areas of urethra, bladder, prostate, seminal vesicles, testes, and vas deferens 43
  • 44.
    2. Psychic elementof sexual stimulation  Can greatly enhance the ability of a person to perform the sexual act  Can even result in nocturnal emissions during dreams, often called “wet dreams,”  So it can be initiated by either ◦ Psychic stimulation from the brain or ◦ Actual sexual stimulation from the sex organs, but ◦ Usually it is a combination of both Integration of the male sexual act in the Spinal Cord  Male sexual act is mainly integrated in the spinal cord (sacral and lumbar spinal cord) 44
  • 45.
    STAGES OF THEMALE SEXUAL ACT Penile Erection - Parasympathetic Nerves  Is the first effect of male sexual stimulation,  Degree of erection is proportional to degree of stimulation,  Release of nitric oxide and/or vasoactive intestinal peptide  Relaxation of the arteries of the penis and the trabecular meshwork of smooth muscle fibers in the erectile tissue of the corpora cavernosa and corpus spongiosum 45
  • 46.
     The erectiletissue consists of large cavernous sinusoids that are normally empty of blood  But become dilated when arterial blood flows rapidly into them under pressure while the venous outflow is partially occluded  The two corpora cavernosa, are surrounded by strong fibrous coats; therefore,  High pressure within these sinusoids causes ballooning of the erectile tissue  Then the penis becomes hard and elongated – erection 46
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    Lubrication - ParasympatheticNS  During stimulation, the PNS impulses stimulate the urethral and bulbourethral glands to secrete mucus.  This mucus flows through the urethra during intercourse to aid in lubrication during coitus  But, most of the lubrication of coitus is provided by the female sexual organs  Without adequate lubrication, intercourse causes grating and painful sensations that inhibit sexual sensations 48
  • 49.
    Emission and Ejaculation– Sympathetic NS  Final stages of sexual act  When the sexual stimulus reaches it’s climax, sympathetic impulses start to be emitted from the reflex centers of the spinal cord  It leaves the cord at T12 - L2 and pass to the genital organs through the hypogastric and pelvic sympathetic nerve plexuses 49
  • 50.
    Emission;  Begins withcontraction of the vas deferens and the ampulla to cause expulsion of sperm into the internal urethra.  Then, contractions of the muscular coat of the prostate gland followed by contraction of the seminal vesicles expel prostatic and seminal fluid also into the urethra.  All these fluids mix in the internal urethra with mucus secreted by the bulbourethral glands to form the semen.  This all is the process of emission. 50
  • 51.
    Ejaculation;  The fillingof the internal urethra with semen elicits sensory signals that are transmitted through the pudendal nerves to the sacral regions of the cord, giving the feeling of sudden fullness in the internal genital organs.  These sensory signals further excite rhythmical contraction of the internal genital organs and cause contraction of the ischiocavernosus and bulbocavernosus muscles that compress the bases of the penile erectile tissue. 51
  • 52.
     These togetherincreases the pressure in the erectile tissue of the penis, genital ducts and urethra  This helps “ejaculate” the semen to the exterior - ejaculation  At the same time, rhythmical contractions of the pelvic muscles and some of muscles of the body trunk causes  Thrusting movements of the pelvis and penis, which also help propel the semen into the deepest recesses of the vagina 52
  • 53.
     This entireperiod of emission and ejaculation is called the male orgasm.  At its termination, the male sexual excitement disappears almost entirely within 1 to 2 minutes and erection ceases, a process called resolution. 53
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    Secretion of Testosterone The testes secrete several androgens which are also called male sex hormones  These including testosterone, dihydrotestosterone, and androstenedione  Testosterone is more abundant and considered as the primary testicular hormone  But, much of the testosterone is eventually converted into the more active hormone dihydrotestosterone in the target tissues 54 TESTOSTERONE AND OTHER MALE SEX HORMONES
  • 55.
     Testosterone isformed by the Leydig cells  Leydig cells; ◦ Found in the interstices between the seminiferous tubules and ◦ Constitute about 20% of the mass of the adult testes ◦ Are numerous in newborn in the first few months of life and after puberty ◦ Are less easily destroyed by x-ray or excessive heat 55
  • 56.
     Androgens arealso produced elsewhere in the body besides the testes 1. Adrenal gland ◦ But it doesn’t have significant masculinizing effect ◦ However, in tumorous conditions significant amount may be produced and cause male secondary sexual characteristics, even in the female 2. Ovary also produces minute/insignificant quantities of androgens  All androgens are steroid and can be synthesized either from cholesterol or directly from acetyl coenzyme A. 56
  • 57.
     About 97%of testosterone becomes either ◦ Loosely bound with plasma albumin or ◦ More tightly bound with beta globulin and ◦ Circulates in the blood in these states for 30 minutes to several hours.  Then it is either transferred to the tissues or degraded into inactive products that are subsequently excreted  Much of the testosterone fixed to the tissues is converted to dihydrotestosterone, especially in certain target organs 57 Metabolism of Testosterone
  • 58.
     The testosteronethat does not become fixed to the tissues is rapidly converted in to other forms mainly by the liver  Then excreted either into the gut by way of the liver bile or into the urine 58
  • 59.
    Estrogen production  Smallamounts of estrogens are also formed in the male (about 1/5th of non-pregnant female)  The exact source isn’t known, but the following are the possible sources: 1. Conversion of testosterone to estradiol by Sertoli cells 2. Formation of estrogen from testosterone and androstanediol by other tissues (liver) 59
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     Generally, testosteroneis responsible for masculinization of the body Functions of Testosterone During Fetal Development  Is responsible for the development of the male body characteristics, including the formation of a penis and a scrotum  It also helps formation of prostate gland, seminal vesicles, and male genital ducts  It also suppresses the formation of female genital organs.  Testosterone is the main stimulus for decent of testes 61 FUNCTIONS OF TESTOSTERONE
  • 62.
    Effect on Developmentof Adult Primary and Secondary Sexual Characteristics  After puberty, testosterone cause the penis, scrotum, and testes to enlarge about eightfold before the age of 20 years.  Causes the secondary sexual characteristics of the male to develop, starting from puberty  Also causes growth of hair in different body parts; pubis, linea alba, face, chest, … 62
  • 63.
     Testosterone causesmale pattern baldness  Testosterone also causes masculine voice (causes hypertrophy of the laryngeal mucosa and enlargement of the larynx)  Testosterone increases thickness of skin and contribute to the development of acne  Testosterone increases protein formation and muscle development 63
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     Testosterone increasesbone matrix and causes calcium retention  Testosterone increases the basal metabolic rate  Testosterone increases red blood cells  Effect on electrolyte and water balance ◦ Has a little effect on electrolytes, but still increases ◦ Blood and ECF volume (increases by 5-10% of body wt) 64
  • 65.
     Most ofthe effects result basically from increased rate of protein formation  So basically testosterone enters the cell and is converted to dihydrotestosterone with the action of 5α-reductase  This in turn binds with cytoplasmic receptor protein and enters the nucleus  Then it binds with nuclear protein to induce DNA-RNA transcription  Then RNA concentration increases which progressively rising the cellular proteins  The number of DNA also rises increasing the number of cells too 65 BASIC INTRACELLULAR MECHANISM OF ACTION OF TESTOSTERONE
  • 66.
    GnRH;  Is secretedby neurons in the hypothalamus and released into the hypothalamic-hypophysial portal vascular system.  GnRH is then transported to the anterior pituitary gland in the hypophysial portal blood  Then it stimulates the release of the two gonadotropins, LH and FSH 66 CONTROL OF MALE SEXUAL FUNCTIONS BY HORMONES FROM THE HYPOTHALAMUS AND ANTERIOR PITUITARY GLAND
  • 67.
     GnRH issecreted for a few minutes at a time once every 1-3 hours – pulsatile release of GnRH  It’s secretion is determined by 1) The frequency of these cycles and 2) The quantity of GnRH released in each cycle  The rate of FSH release is slightly affected by this pulsatile release of GnRH, rather  It changes more slowly over a period of many hours in response to long term changes in GnRH 67
  • 68.
     But, thesecretion of LH is also cyclical, which follows the pulsatile release of GnRH.  Because of this closer relation between GnRH and LH secretion, GnRH is also widely called LH-releasing hormone 68
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    Gonadotropic Hormones: LHand FSH  These are glycoprotein hormones secreted by the same cells of anterior pituitary gland, called gonadotropes.  Almost no LH or FSH are secreted in the absence of GnRH  Testosterone secretion by Leydig cells only occurs when stimulated by LH from the anterior pituitary gland and  The rate of secretion is almost proportional and  Anterior pituitary gland secretion of LH and FSH is inhibited by testosterone-Negative feedback control 70
  • 71.
    Role of FSHand Testosterone on Spermatogenesis  Both FSH and testosterone are obviously necessary for spermatogenesis  FSH binds with specific FSH receptors at the Sertoli cells  This causes the Sertoli cells to grow and secrete various spermatogenic substances.  Simultaneously, testosterone (and DHT) diffusing into the seminiferous tubules also  Cause strong tropic effect on spermatogenesis 71
  • 72.
    Role of Inhibinin Negative Feedback Control  This hormone has a strong direct effect on the anterior pituitary gland to inhibit the secretion of FSH  It operates with and in parallel of the negative feedback mechanism for control of testosterone secretion 72
  • 73.
    Human Chorionic Gonadotropin Secreted by the placenta and circulates both in the maternal and fetal circulation  Stimulates testosterone secretion by the fetal testes  Has almost the same effects on the sexual organs as LH 73
  • 74.
    Female Physiology Before Pregnancyand Female Hormones By; T/berhan H. MSc in Medical Physiology
  • 75.
    Composed of;  Gonads; ◦Ovaries  Reproductive tract; ◦ Uterine (fallopian) tube ◦ Uterus ◦ Vagina  External genitalia ◦ vulva;  Vaginal opening  Clitoris  Labia minora/majora  Accessory glands ◦ Vestibular glands Functions; ◦ Production of ova (oogenesis) ◦ Reception of sperm from male ◦ Transport of ova ◦ Maintenance of developing fetus ◦ Childbirth (parturition) 75 Female reproductive system
  • 76.
    Female reproductive system Composedof; • Gonads; – Ovaries • Reproductive tract; – Uterine (fallopian) tube – Uterus – Vagina • External genitalia – vulva; • Vaginal opening • Clitoris • Labia minora/majora • Accessory glands – Vestibular glands Functions; • Production of ova (oogenesis) • Reception of sperm and fertilization • Transport of ova • Maintenance of developing fetus • Childbirth (parturition) 76
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    OOGENESIS AND FOLLICULAR DEVELOPMENT •Oogenesis; differentiation of developing egg (oocyte) into a mature egg (ovum) • Starts with migration of primordial germ cells First from the dorsal endoderm of the yolk sac to the outer surface of the ovary – with repeated cell division Then further into the substance of the ovarian cortex - now called oogonia or primordial ova 79
  • 80.
    ….cont • Then eachoogonia collects spindle cells from the ovarian stroma around it and • These cells take on an epithelioid characteristics which are then called granulosa cells. • The ovum at this stage is now called primordial follicle (primary oocyte) • By the fifth month of fetal development, the oogonia completes mitotic replication and prophase I 80
  • 81.
    …cont • From then,mitotic cell division ceases and no additional oocytes are formed • At birth there are about 1 to 2 million primary oocytes At puberty • Meiotic cell division of the oocyte continues and completes meiosis I • So, each oocyte divides and gives a large secondary oocyte (ovum) and a small first polar body where both containing 23 pairs of chromosomes 81
  • 82.
    ….cont • The firstpolar body disintegrates with/without second meiotic division • The ovum then starts second meiotic division, and paused at metaphase II • If fertilization occurs meiosis II will continue and complete it’s stages • Half of the sister chromatids remain in the fertilized ovum and the other half are released in the second polar body 82
  • 83.
    ….cont • At puberty,only a small percentage of the only 300,000 oocytes remained in the ovaries become mature • Out of these, only 400 to 500 of the primordial follicles develop enough to expel their ova (one each month) during reproductive life (13-46 years of age) • The remaining thousands of oocytes degenerate 83
  • 84.
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    FEMALE HORMONAL SYSTEM Consistsof three hierarchies of hormones • Hypothalamic hormone - GnRH • Anterior pituitary hormones – FSH and LH • Ovarian hormones - estrogen and progesterone Secretion; • GnRH is secreted in short pulses once every 90 minutes like in males • But the secretion rate of the other hormones during the monthly sexual cycle is quite different 85
  • 86.
  • 87.
    MONTHLY OVARIAN CYCLE; •Average monthly sexual cycle is 28 days (20-45) • Two importance; 1. Release of single ovum each month 2. Preparation uterine endometrium for implantation The monthly ovarian changes are completely due to the gonadotropic hormones, FSH and LH In the absence of these hormones, the ovaries remain inactive Starts at puberty (age of 11-15 years) 87
  • 88.
    1) FOLLICULAR PHASEOF THE OVARIAN CYCLE • At birth each ovum is surrounded by a single layer of granulosa cells – which is called primordial follicle • Till puberty the granulosa cells; 1. Provide nourishment and 2. Secrete an oocyte maturation inhibiting factor (that keeps them in prophase I) 88
  • 89.
    • At puberty;higher amount of FSH and LH is secreted • The ovaries with some of the follicles within it begin to grow • The first stage of follicular growth begins with Moderate enlargement of the ovum, (twofold to threefold) Growth of additional layers of granulosa cells Which are now called primary follicles 89
  • 90.
    Development of Antraland Vesicular Follicles • FSH, cause accelerated growth of 6 - 12 primary follicles each month • Rapid proliferation of the granulosa cells, giving rise to many more layers • Then spindle cells (from the ovary interstitium) collect around the granulosa cells, giving rise to a second mass of cells called the theca 90
  • 91.
    • Theca hastwo cell layers 1. Theca externa – is the outer layer  Develops into a highly vascular connective tissue capsule  Becomes the capsule of the developing follicle 2. Theca interna – inner layer  Develops an epithelioid nature like the granulosa cells and  Develop the ability of secreting additional steroid sex hormones (estrogen and progesterone) 91
  • 92.
    • After daysof proliferative phase of growth, granulosa cells secretes a follicular fluid that contains a high concentration of estrogen • As a result an antrum appears within the mass of granulosa cells • This whole growth of primary follicle up to the antral stage is stimulated by FSH alone 92
  • 93.
    • Then evenlarger follicles called vesicular follicles develops more rapidly as a result of; 1. Increased number of FSH receptors formed by granulosa cells due to the secretion of estrogen in to the follicle. This makes the granulosa cells even more sensitive to FSH – positive feedback 2. Both FSH and estrogen promote LH receptors on the granulosa cells, allowing LH stimulation and creating an even more rapid increase in follicular secretion. 3. The increased estrogen and LH act together to cause proliferation of the follicular thecal cells and increase their secretion as well. 93
  • 94.
    • Then antralfollicles begin to grow rapidly • The ovum itself enlarges with about 3-4 fold in diameter, resulting in total increase of up to 10-fold, or a mass increase of 1000-fold. • As the follicle gets enlarged, the ovum is kept at one pole of the follicle surrounded in a mass of granulosa cells. 94
  • 95.
    • Only onefollicle fully matures each month – Outgrowth of one follicle and atresia of the other all (5 - 11 developing follicles), and the probable reason is – The negative feedback of estrogen from the most rapidly growing follicle causing on hypothalamus, where – The largest follicle continues to grow due to its intrinsic positive feedback effects – This is important because it prevents development of more than one child in each pregnancy – At ovulation, only a single follicle matures with a diameter of 1 - 1.5 cm & called the mature follicle 95
  • 96.
  • 97.
    Ovulation • Through theprocess of rapid follicular development a protruding outer wall of the follicle begins to swell like a nipple called stigma • Then, fluid begins to ooze from the follicle through the stigma, that later ruptures widely and allowing a more viscous fluid, which has occupied the central portion of the follicle, to evaginate outward. • This fluid carries with it the ovum surrounded by corona radiata (mass of several small granulosa cells). • Ovulation occurs 14 days after the onset of menstruation in a woman with 28-days of female sexual cycle. 97
  • 98.
    A surge ofLH is needed for ovulation • 2 days prior to ovulation, LH secretion rises 6 - 10 fold & peaks about 16 hours before ovulation • Similarly FSH increases 2-3 fold and • Both FSH and LH act synergistically to cause rapid swelling just a few days before ovulation. • The LH also causes the granulosa and theca cells mainly secrete progesterone • As a result rate of estrogen secretion falls about 1 day before ovulation 98
  • 99.
    Initiation of ovulation •LH causes the rapid secretion of follicular steroid hormones mainly containing progesterone • This in turn causes two main events to happen which are important for ovulation: 1. Release proteolytic enzymes from lysosomes by theca externa  Causing degeneration and weakening of the stigma wall and  Further swelling of the entire follicle 2. Rapid growth of new blood vessels into the follicle wall, and secretion of prostaglandins (local vasodilators) • As a result of these two events there will be transudation of plasma into the follicle that furthers add to the swelling • Finally, the follicular swelling & degeneration of the stigma causes rupture of the follicle and discharge of the ovum. 99
  • 100.
  • 101.
    2) LUTEAL PHASEOF THE OVARIAN CYCLE • After a few hours of ovum expulsion, the remaining granulosa and theca interna cells change rapidly into lutein cells • These cells enlarge in diameter (>2x) and become filled with lipid inclusions that give them a yellowish appearance • This process is called luteinization, and the total mass of cells together is called the corpus luteum • A well-developed vascular supply also grows into the corpus luteum 101
  • 102.
    • The granulosacells in the corpus luteum form large amounts of the female sex hormones progesterone and estrogen (more progesterone than estrogen) and • The theca cells form mainly androgens (androstenedione and testosterone) • However, most of these hormones are converted into estrogens by the aromatase enzyme in the granulosa cells 102
  • 103.
    • The corpusluteum will have about 1.5 cm of diameter after 7 - 8 days of ovulation. • Afterwards it begins involute and eventually loses its – Secretory function – Yellowish and lipid characteristic and – Becomes the corpus albicans that is replaced by connective tissue which is finally absorbed 103
  • 104.
    Luteinizing Function ofLH ; • LH is responsible for the conversion of granulosa and theca interna cells into lutein cells • This function gives LH its name - “luteinizing,” for “yellowing” • Until ovulation local hormone in the follicular fluid, called luteinization-inhibiting factor, hold the luteinization process in check 104
  • 105.
    Secretion by theCorpus Luteum (role of LH): • Corpus luteum is a highly secretory organ, that continues to secrete large amounts of progesterone and estrogen • Once LH (mainly secreted during the ovulatory surge) has acted on the granulosa and theca cells, • The newly formed lutein cells seem to be programmed to go through predetermined sequence of 1. Proliferation 2. Enlargement, and 3. Secretion, followed by 4. Degeneration • All this occurs in about 12 days. 105
  • 106.
    Involution of CorpusLuteum and onset of next ovarian cycle 1. Estrogen in particular and progesterone to a lesser extent, have strong feedback effects in maintaining low levels of FSH and LH 2. Similarly inhibin hormone secreted by lutein cells also inhibits FSH secretion • Both thess causes low secretory rates of FSH and LH • Low or total loss of FSH and LH finally causes the corpus luteum to degenerate completely • This process called involution of the corpus luteum. 106
  • 107.
    • This happensat the end of 12th day of corpus luteum life (26th day of the sexual cycle) which is 2 days before menstruation begins. • The sudden cessation of estrogen, progesterone, and inhibin secretion by the corpus luteum removes the feedback inhibition of the anterior pituitary gland, • This results in the secretion increased amounts of FSH and LH again and • Beginning of new ovarian cycle 107
  • 108.
    Monthly Uterine Cycle •Refers to cyclical changes in the endometrial lining of the uterus • Resulting in an overt bleeding from the genital tract • Also called endometrial cycle • Is the period between menstrual flows • Involves cyclic rise and fall in female reproductive hormones • Is variable at the extremes of reproductive ages Rationale • Periodic preparation for fertilization + pregnancy 108
  • 109.
    A. Proliferative Phase(Estrogen phase)  Begins with the last days of menses and ends around ovulation  Dominant ovarian hormone: estrogen Main events; a. Stroma & epithelium: •↑ Proliferation and growth of epithelial + stromal cells. •At the time of ovulation the endometrium regains its thickness (3 - 5 mm thick) b. Glands: • Progressive growth of endometrial glands • Cervical epithelium secrets a thin, watery mucus c. Angiogenesis: • Lengthening of the vessels • Neovascularization of layers d. Receptors: • ↑Estrogen + progesterone receptors on endometrial cells 109
  • 110.
    110 Uterine gland Uterine artery Uterinelumen Organization of glands and blood flow within the uterine endometrium
  • 111.
    B. Secretory Phase(Progestational Phase) a. Duration: 14th - 28th day. b. Predominant hormone: • Progesterone (10x, corpus luteum). • Estrogen c. Epithelium and stroma: • Marked secretory changes and swelling of the endometrium • Further thickening of endometrium • All these changes are important for implantation of fertilized ovum • ↑ Adhesivity of surface epithelium. d. Mucous glands: • Elongation and coiling • Secrete thick viscous fluid • Glycogen • Cervical mucus becomes thick f. Angiogenesis: ` • Spiraling of the blood vessels • ↑ Vascularity g. Receptors: • ↓ Number of estrogen + progesterone receptors. 111
  • 112.
    Organization of glandsand blood flow within the uterine endometrium 112
  • 113.
    C. Menstrual Phase I.If no fertilization + no production of hCG, CL involutes →↓E, P (Luteolysis/luteal regression). Then 3 events follows to cause menstrual bleeding a. ↓ E, P → ↓ stimulation of endometrial cells → rapid involution of the endometrium → ↑ local Pgs b. Then, vasospasm of the tortuous blood vessels (due to Pgs) → ↓nutrients → ischemia and necrosis → formation of hemorhagic and edematous layer, then c. Desquamation and separation of the necrotic outer layer → initiation of uterine contractions that expel the uterine contents → bleeding II. If conception occurs: the functional life span of corpus luteum is extended (due to hCG) 113
  • 114.
  • 115.
    115 Normal menstrual cycle: a.Duration: 2-8 d b. Cycle length: 21-35 d (28 + 7) c. Vol. blood loss: 20-150ml (aver. 50ml). d. Type of blood flow: 75% arterial, 25% venous. e. Contents: tissue debris, Pgs, fibrinolysin f. No clot formation: but, (if no fibrinolysin + excessive bleeding → clot formation)
  • 116.
    116 Cervical Cycle Quantity +quality of mucus is changed i. E: → Profuse, watery, alkaline (penetrability by sperm is maximal) ii. P: scanty, viscous, infiltration with cellular elements Vaginal cycle i. E: ↑Cornification (hardening), ↑ acidophilic cells (Pap smear) ii. P: Thick mucus, infiltration with PMNL, ↓acidophilic cells
  • 117.
    117 Cyclic Changes inthe Breasts • E: Proliferation of mammary ducts. • P: causes growth of lobules and alveoli. • Distention of ducts/hyperemia + edema → breast swelling, tenderness & pain.
  • 118.
    118 The cycle ofovulation and menstruation
  • 119.
    119 Physiological and behavioralvariables 1. Core body temperature • 0.5°C in the luteal phase/oral or rectal. • Progesterone/resetting thermostat center + thermogenic effect. 2. Sensory acuity • Olfactory acuity (menstrual synchronization). 3. Sexual activity • Human female sexual behavior around the mid-cycle ( Androgens) 4. Eating behavior and body weight •  Food intake in luteal phase ( 5-HT activity).
  • 120.
    120 Hypothalamic – Hypophyseal- Ovarian Axis Purpose a. Production of physiologic quantities of sex steroids b. Generation of healthy ova that become mature female gamets
  • 121.
    121 Components a. Hypothalamic GnRH/LHRHHypophysis Neural b. Hypophyseal Gns Ovary LH, FSH c. Ovary i. Granulosa cells Estradiol/inhibin/activin ii. Thecal cells Androgens/estradiol  Negative feedback  Positive feedback control
  • 122.
  • 123.
  • 124.
    124 Hypothalamus GnRH Gonadotropes LH FSH Theca cellsGranulosa cells Androgens Inhibin + ¯ + + + Estradiol ¯ ¯ Chronic illness Weight & fat loss Stress, drugs, exercise ¯ GnRH analogues • Breast Ca. • Endometriosis • Leiomyomas Summary of H-P-O axis
  • 125.
    The Physiology ofOvarian Hormones 1) Estrogens (17β-estradiol, estrone, estriol) a. Biosynthesis; Origin: Ovary: granulosa cells + theca cells Corpus Luteum Placenta/pregnancy Adrenal cortex Testis (Males: Sertoli cells, aromatization) Chemistry Precursors: Cholesterol/C-27 Animal fat in the diet, De Novo synthesis. 125
  • 126.
    b. Secretion andbioavailability; •98% is found bound to carrier proteins. 38% to sex hormone binding globulin (SHBG) 60% to plasma albumin •2% exist in free form. c. Metabolism: Liver → bile, urine 126
  • 127.
    2) Progestins: Progesterone 17α-hydroxyprogesterone Origin:Ovarian follicles Corpus luteum Placenta/pregnancy Adrenal cortex Testes/males 127
  • 128.
    Synthesis • Cholesterol (C-27)→ C-21 steroid Bioavailability •Bound to: 80% to albumin 18% transcortin (CBG) 2% Free Metabolism: Liver (urine) 128
  • 129.
    The Physiological adjustmentsto Pregnancy a. Amenorrhea b. Morning sickness •4th -5th week of pregnancy/peak at the 8th week. • Disappears at 14th week. •??? hCG •??? Steroids of pregnancy→↓ Intestinal motility 129
  • 130.
    130 c. Enlargement ofreproductive tract •Ovary: ↑ size/∵ CL of pregnancy. •Uterus: 50gm → 1100gm (volume = stretching + hypertrophy). • Cervix: ↑ • Vagina + vulva: ↑ •Breasts: ↑ (2x) d. Acromegalic features e. Weight gain:  11-12.5kgs oFetus = 3.5kgs oAmniotic fluid, placenta + fetal membranes = 2kgs oUterus = 1kg oBreasts = 1kg oBlood & ECF = 2.5kg oFat = 1 kg
  • 131.
    131 • ↑Appetite +food intake/hormonal + flow of substrates from the maternal blood to the fetus f. BMR: ↑10-15% (↑T4 , ↑sex steroids, ↑adrenocortical hormone). (To supply energy that is expended to carry the extra load.) g. Hematological changes: •  Blood volume: 40-45% (Plasma volume +RBC mass/450ml, plasma>RBC) • ↑Plasma volume → haemodilution → Physiological anaemia (↓ RBC count, ↓ Hb, ↓ Hct). • ESR (plasma globulins, fibrinogen). •  Fe requirement
  • 132.
    Significance of volumeexpansion: • It meets the metabolic demands of the enlarged uterus and its greatly hypertrophied vascular system. • It provides abundant nutrients and elements to support the rapidly growing placenta and fetus. • It protects the mother, and in turn the fetus, against the deleterious effects of impaired venous return in erect positions. • It safeguards the mother against the adverse effects of parturition- associated blood loss. 132
  • 133.
    Δs in totalblood volume + plasma + RBC volumes during pregnancy 133
  • 134.
    134 h. Cardiovascular • ↑CO (35%, 27wks) → ↑ HR, ↑SV (Placenta: A-V shunt). • ↑ Venous return • ↑ Blood flow: lungs, skin, kidneys, GIT, coronaries and breasts). • ↑ Blood volume: 1-1.5l • ↑ Uteroplacental blood flow: uterus, placenta/625ml/min.
  • 135.
    I. Renal • ↑GFR/50% → ↑ Urine output i. Hypervolemia-induced haemodilution lowers the protein concentration and oncotic pressure of plasma entering the glomerular microcirculation. ii. Renal plasma flow increases by approximately 80% • Gravid uterus compresses the bladder + ↓volume capacity → ↑frequency of urination 135
  • 136.
    136 Cardiovascular and renalchanges in pregnancy
  • 137.
    J. Respiration • ↑O2 requirements (30%). • ↑ Minute ventilatory volume/↑30-50% i. To supply the fetus + to support the increased metabolic rate. ii. Progesterone increases sensitivity of respiratory chemoreceptors to CO2 + ventilation is adjusted to keep the arterial PCO2 lower than normal. • ↑ Tidal volume, inspiratory capacity •  Peak expiratory flow rate 137
  • 138.
    • Airway conductance,Total pulmonary resistance. • ↓ Functional residual capacity (↓Expiratory reserve +↓Residual volume). • ↓ Total lung volume, ↓ Inspiratory reserve. • Total lung capacity remains unchanged. • Expanding uterus pushes the abdominal viscera up against diaphragm and interferes with breathing/↑RR. 138
  • 139.
    k. Immune system •Cell-mediated immunity is suppressed (Maintenance of pregnancy + protection of the fetus, progesterone). l. GIT • ↑ Gastric emptying time, ↓ intestinal motility → constipation (↑ Progesterone). • ↓ lower esophageal sphincter tone → reflux esophagitis or ‘Heartburn’ (↑ Progesterone). 139
  • 140.
    140 m. Integumentary system I.Hyperpigmentation (   MSH). • ↑ Melanocyte activity: Darkening of the areola. Linea nigra (mid line below umbilicus) • Temporary darkening of the skin (nose, cheeks – ‘Mask of pregnancy’, chloasma).  ↑ Gravid uterus→ stretching the dermis-tears the collagen tissue → striae gravidarum/reddish → silver white/ II. Vascular changes (hyperestrogenemia). • Angiomas/spider angiomas (face, neck, upper chest, and arms). • Palmar erythema
  • 141.
    141 n. Endocrine system i.Anteriorpituitary • ↑ 50% increment in size, ↑ TSH, ↑ Prolactin. • ↓ FSH, LH/∵ inhibitory effect of E + P from the placenta. • ↓ GH ii. Adrenal cortex • ↑Plasma glucocorticoids • ↑ Aldosterone/2x → ↑ salt + H2 O retention/hypertension.
  • 142.
    142 iii. Thyroid Gland(↑50%) • ↑TSH → ↑ T3 , T4 → ↑ BMR iv. Parathtyroid Glands • ↑ Size → ↑ PTH → mobilize Ca2+ from the mother’s bone to make it available to the fetus
  • 143.
    143 v. Relaxin (CorpusLuteum & placenta) a.Remodeling of the pelvic girdle, softening of the Cx + the vagina b.Cervical softening, effacement + dilatation, decrease time to delivery c.Laxity of pelvic joints and separation of the pubic symphysis d.Relaxin + Progesterone → inhibit myometrial contractions → quiescence → maintenance of pregnancy
  • 144.
    The Endocrine Placenta PlacentalFunctions: Respiratory, Nutritive, Excretory, Endocrine o Maintains a quiescent gravid uterus o Maternal physiology to ensure fetal nutrition in utero. o Maternal pituitary function + mammary gland development o Determines the time of labor and delivery. o Source of hCG 144
  • 145.
    145 Role of theplacenta in exchanges between the fetal & maternal compartments
  • 146.
    146 Peptide hormones: hCG+ hPL Others: Relaxin, inhibin, GnRH, ACTH, CRH, TRH, IGFs β-endorphin,
  • 147.
    147 Human chorionic gonadotropin(hCG) • Origin: syncytiotrophoblast of the placenta. • Synthesis: glycoprotein, 236aa, 38kd, 2 noncovalently linked subunit (α, β) • Homology: LH, FSH, TSH (Luteinizing + Luteotropic). • Secretion and plasma o 6-8d after conception o Peak: 60-90d o Plateauing: 120d before delivery. o After delivery: 12-24hrs.
  • 148.
    o ↑ hCG:Multiple pregnancy Rh – isoimmunization Diabetic woman in pregnancy Choriocarcinoma o  hCG: Ectopic pregnancy Miscarriage ….???abortion 148
  • 149.
    149 • Function: a. Maintainthe early corpus luteum of pregnancy (LH). b. Promote steroidogenesis. c. Regulate the development + secretion of T by the fetal testes d. Give immunological privilege to the developing trophoblast.
  • 150.
    150 Circulating levels ofhCG in maternal blood during pregnancy.
  • 151.
    151 Human Placental Lactogen(hPL, CGP, hCS) •Origin: syncytiotrophoblast •Chemistry: a single chain polypeptide •Homology: GH •Secretion & Plasma o 3rd week after conception. o Appears at plateau at term. o [hPL]  placental weight. •Nature o Mainly - lactogenic activity o 3% - growth promoting activity o t½ = 20min (it can not be detected after birth).
  • 152.
    152 • Functions a. Sparesmaternal glucose → providing continued nutrition for the developing fetus (insulin-resistance state). b. hPL exerts metabolic effects in pregnancy similarly to those of GH. i. Stimulation of lipolysis → ↑ free FA (accelerated starvation). ii. Inhibition of glucose uptake in the mother → development of maternal insulin resistance (diabetogenic). iii. Inhibition of gluconeogenesis →↑ transportation of glucose and protein to the fetus.
  • 153.
    Placental Steroid Hormones 1.Progesterone •Source and synthesis: maternal cholestrol, trophoblast •Functions: a.Progesterone binds to receptors in uterine smooth muscle →↓RMP → inhibiting smooth muscle contractility →myometrial quiescence → prevents premature expulsion of fetus b. Secretory endometrium → decidua/histiotropic + hemotropic nutrition. c. Inhibits Pgs formation and other paracrine factors d. Maintenance of pregnancy: inhibit T-lymphocyte cell-mediated response e. Breasts: lobuloalveolar development. 153
  • 154.
    154 Maternal serum levelof progesterone during pregnancy
  • 155.
    155 2. Estrogen •Origin: Corpusluteum (early wks of preg.) + syncytiotrophoblast •Urinary estriol excretion of the mother → index of the state of the fetus •It should be steadily increasing throughout pregnancy if the fetus is growing normally Functions: a. Stimulate Pg synthesis •↑ Uterine blood flow (↑fetal organ maturation + development) b. Mediate the growth + development of the maternal reproductive organs c. Stimulates phospholipid synthesis + turnover
  • 156.
    156 Maternal serum levelsof estrogens during pregnancy
  • 157.
    157 Secretion rates ofplacental hormones
  • 158.
    The Physiology ofParturition 1. Defiition  delivery of the baby •Duration of gestation; 40wks 2. Mechanisms: not known completely  Mechanical factors a.Distension of uterus (fetal age size) → ↑ stretching of smooth muscle, inherent rhythmicity) → ↑ contractility. 158
  • 159.
    b. Uterine contractions(Braxton Hicks contractions +ve feedback) ↑ Distension + effect of hormones ↓ Uterine contractions ↓ The increased pressure of the baby’s head against the cervix with each contractions excites the fundus or body of the cervix to contract ↓ Dilatation of cervix & distension of vagina. ↓ Stimuli from the cervix + vagina ↓ ↑ Secretion of oxytocin ↓ ↑ Uterine contraction until they are strong enough to expel the baby 159
  • 160.
     Neuroendocrine factors a.Progesterone withdrawal •↓ P at the end of gestation period →↓No. of myometrial progesterone receptors •↓ Antagonistic effect of progesterone to oxytocin + Pgs •↓ Progesterone → synchronizing uterine contractions 160
  • 161.
    161 b. Estrogen •↑ E(in amount) →↑ prostaglandin synthase activity in the tissues of the uterus + fetal membrane →↑ myometrial contractions. •↑ E →↑ myometrial + endometrial oxytocin receptors. •↑ E →↑ oxytocin production & secretion by the neurohypophysis c. Oxytocin •↑ Uterine contractions/distension + E. •↑ Oxytocin →↑Pg → stimulate uterine smooth muscle contraction → expulsion of the fetus
  • 162.
    162 d. Relaxin •Relaxes thepubic ligaments + relaxes the lower part of the uterus. •Ripen/soften cervix → so eases the passage of the offspring at birth. •↑ Sensitivity of the uterus to oxytocin. e. Prostaglandins •↑ E →↑Pg synthesis →↑ Intracellular Ca2+ in the myometrium → uterine contractions •Act synergistically with oxytocin/cervical ripening, softening, dilatation, contractions
  • 163.
    3. Mechanics ofLabor a.Uterine contractions begins at the fundus + spread downward over the body of the uterus b. Intensity of contraction is stronger at the fundus than in the lower segment of the uterus - force the baby downward toward the cervix c. Frequency of contractions: onset: once in every 30min later: once in 1 to 3 min.  Intermittent contraction will not stop the blood flow thru the placenta and the fetus will not die. 163
  • 164.
    164 d. Stages • 1st stage:the period from onset of labor up full cervical dilatation - (8-24hrs or less) • 2nd stage: the time interval from the full dilatation of the cervix till delivery of fetus (hrs to minutes) • 3rd stage: the time taken for separation and delivery of the placenta (10-45min) • Duration of each stage tends to be longer in a primipara than in a multipara
  • 165.
    The Mammary Glandsand Lactation • Mammary glands: replaces the nourishing function of the placenta after birth. • Lactation → evolutionarily conserved mammalian physiological function. 1. Mammogenesis • Puberty: ↑ Estrogen → duct growth ↑ Progesterone→ lobuloalveolar growth Permissive role: GH + glucocorticoids + PRL + Insulin. • Pregnancy: milk secretion doesn’t occur (Inhibition of placental E + P) Following delivery placental E+P ↓→ lactation begins 165
  • 166.
    166 2. Lactation a. Milksynthesis: initiated during the end of pregnancy/PRL, hPL b. Lactogenesis: synthesis of milk by alveolar cells & its secretion is initiated by the loss of placental steroids after birth. c. Galactopoiesis: maintenance of established lactation, controlled by PRL d. Milk ejection: passage of milk from alveolar lumen to the duct system and collection in the ampulla and larger ducts delivery to the infant • Controlled by oxytocin.
  • 167.
    Relationship of thealveolar lobules and duct system Arrangement of alveoli in a mammary lobule. 167
  • 168.
    3. Milk EjectionReflex Nipples (Mechanoreceptors → suckling) ↓ Somatic touch pathways (multisynaptic pathway) induced ↓ Signals sent to Hypothalamic nuclei (SON, PVN) ↓ Oxytocin neurons release oxytocin ↓ Induces contraction of myoepithelial cells that surround alveoli and ducts ↓ Mobilization of milk from the alveoli and duct system to the nipple ↓ Producing the sensation of ‘milk let-down’ in the mother. 168
  • 169.
    3.12.3. Milk SecretionReflex Suckling of nipples (mechanoreceptors) ↓ Somatic touch pathways (multisynaptic pathway) ↓ Hypothalamic nuclei ↓ Inhibition of PIH secretion ↓ Secretion of PRL from the anterior pituitary ↓ Stimulation of milk secretion by the mammary glands 169
  • 170.
  • 171.
    171 4. Components ofmilk • Protein: casein, α-lactalbumin, β-lactoglobulin • CHO: lactose, fat, minerals (Ca, Mg, P, Fe). • Electrolytes: Cl- , K+ , Na+ … • Vitamins • Immunoglobulins: IgMs, IgEs, IgAs • Growth factors: EGF, IGF-1…
  • 172.
    172 5. Lactation andMenstrual Cycle • Mothers who do not nurse → menses/6 wks after delivery. • Regular nursing→ amenorrhoeic/25-30wks. • 50% of the cycles in the first 6 months → anovulatory 6. Lactation as a Contraceptive a. Suckling →↑ PRL secretion → inhibits GnRH/LHRH secretion. b. Inhibits the action of GnRH on gonadotropes c. Antagonizes the action of gns in the ovaries.
  • 173.
    FEMALE SEXUAL ACT •Sexual desire is higher during ovulation (may be due to higher estrogen) • Like in males effective sexual act depends on both psychic stimulation and local sexual stimulation • Local sexual stimulation includes – Clitoris – Vulva, vagina, and other perineal regions 173
  • 174.
    • Sexual sensorysignals pudendal nerve and sacral plexus sacral segments of the spinal cord cerebrum • But local integration reflexes in the sacral and lumbar spinal cord are also responsible for some of the reactions 174
  • 175.
    Female Erection andLubrication • Controlled by parasympathetic NS • Identical erectile tissues with the glans penis extends from introitus up to the clitoris undergoes similar events like in males • Vasodilation and accumulation of blood on these areas tightening of introitus 175
  • 176.
    • Parasympathetic NSalso also the bilateral Bartholin glands mucus secretion inside the introitus • Much lubrication is also provided by mucus secreted by the vaginal epithelium 176
  • 177.
    Female Orgasm • Alsocalled female climax • Best achieved from both sexual stimulations • Is analogous to emission and ejaculation in male • Promote fertilization of ovum • Resolution – after sometime of the orgasm 177