Reproductive cycle useful for undergraduate , post graduates and for secondary and higher secondary students science education. It includes physiology of menstrual cycle and role of hormones in mammalian reproductive cycles

1. REPRODUCTIVE CYCLE
Dr. RASHMI A. MOREY
PUNE DISTRICT EDUCATION ASSOCIATION’S
PROF. RAMKRISHNA MORE COLLEGE
AKURDI- PUNE

2. REPRODUCTIVE CYCLES IN MAMMALS
• Sexual reproduction in most species is regulated by regular hormonal
changes, or cycles, in the female.
• These cycles are known to have stages/phases which depict peculiar
physiological events.
• These cycles begin at Puberty, function for variable times and can then
decrease or cease entirely.
• There are a number of different species-specific female hormonal cycles
which regulate reproduction.
• Along with this the completion of such cycles specially in human is know to
be influenced by number of factors like environment, stress, overall body
physiology etc.

3. General Introduction of Reproductive cycle
• In mammals other than human is the estrous cycle (series of physiological uterine, ovarian, and
other changes) which consist of proestrus, estrus, metaestrus, and anestrus or diestrus).
• The breeding periods or reproductive receptivity in adult females, other than primates, is
called estrus
• In humans there is Menstrual cycle (period in which the ovum matures, ovulated, and enters
the uterine lumen via the uterine tubes)
• It involve activities of the hypothalamus, hypophysis, ovaries, uterus, uterine tubes and
mammary glands
• It prepare the reproductive system for pregnancy. A hormone-releasing factor synthesized in the
hypothalamus and carried via the hypophyseal portal system of vessels to the anterior lobe of
the hypophysis, causes the cyclic release of the gonadotropic hormones, follicle-stimulating
hormone (FSH), and luteinizing hormone (LH)

4. Menstrual Cycle: What is it?
• This cycle commences at puberty and ends at menopause.
• Its a regular cyclic hormonal change which coordinate changes in the ovary and internal
reproductive tract.
• Human reproduction is regulated in females through the menstrual cycle.
• This is a cyclic endocrine regulated change in female anatomy and physiology that occur
over 28 days (4 weeks, a lunar month) during reproductive life (between puberty and
menopause).

5. Salient features:
• The average menstrual cycle is 28 days with ovulation (egg release) occurring
approximately the middle of the cycle.
• The last menstrual period (LMP) is used clinically in determining developmental
ages.
• Menstruation phase (menses, period) is the loss of the uterus epithelial functional
layer and occurs if fertilization and implantation have not occurred before the end
of the current cycle.
• Menstrual cycle stages can be characterised by Vaginal smear technique, first
devised by Papanicolaou in 1933.
• This cycle differs from other non-primate female vertebrates (eg rats, mice,
horses, pig) that have a reproductive cycle called the estrous cycle.
• It is divided into two phases: follicular or proliferative phase, and the luteal or
secretory phase

6. EARLY FOLLICLE DEVELOPMENT is induced by FSH and Final stages of maturation require LH as well
• In the ovary, the primordial follicles are surrounded by a single layer of granulosa cells.
• After puberty, each primordial follicle enlarges and develops into a preantral follicle
• The preantral follicle is surrounded by several layers of granulosa cells as well as by theca cells.
• The preantral follicle then develops a cavity ,known as an antral follicle.
• The antrum is a fluid-filled space in the secondary (antral) follicle
• Finally, it becomes a preovulatory/Graffian follicle on its way towards ovulation
• At ovulation, fluid is released along with the oocyte
• Growing follicles produce Estrogen (female sex hormone) that regulates development and functions of
reproductive organ
Ovarian Events
# Note !
Theca Interna
(Greek, thek = box) The ovarian follicle endocrine cells forming the inner layer of the theca folliculi
surrounding the developing follicle within the ovary.
Theca Externa
(Greek, thek = box) The ovarian follicle stromal cells forming the outer layer of the theca folliculi surrounding
the developing follicle within the ovary. Consisting of connective tissue cells, smooth muscle and collagen
fibers

7. OVULATION
• Under influence of FSH and LH, around mid cycle or 14 days , the follicle grows rapidly
producing a bulge or cystic swelling on the ovarian surface, and a small oval avascular
spot, the stigma, is seen on the swelling
• Before ovulation, the oocyte and some cells of the cumulus oophorus detach from the
inside of the distended follicle
• At ovulation, there is a "surge" of LH release, the stigma balloons out, forming a surface
vesicle, then it ruptures, expelling the oocyte with follicular fluid
• The oocyte is covered by the zona pellucida and one or more layers of follicular cells
which radially arrange themselves as the corona radiata
• Signs of ovulation include mittelschmerz or intermenstrual pain and basal body
temperature rise (slightly). Although the time; between ovulation and succeeding
menstrual bleeding is constant, the time between ovulation and the preceding
menstruation is highly variable and depends on how long the follicle needs to mature.
One cycle of maturation may need more time than another
• Associated with follicle rupture is movement of the ampulla region of the uterine horn.
Ovarian Events …

8. Ovulation and Hormones
• Hypothalmus releases gonadotropin releasing
hormone (GRH, luteinizing hormone–
releasing hormone, LHRH) -> Pituitary
releases follicle stimulating hormone (FSH)
and lutenizing hormone (LH) -> ovary follicle
development and ovulation.
https://embryology.med.unsw.edu.au/embryology/index.php/Menstrual_Cycle#/media/File:Menstrual_cycle.png

9. • The corpus luteum (Latin, corpus = body, luteum = yellow)
develops from the remains of Graffian follicle after ovulation.
Functions as an endocrine organ (produce progesterone and
oestrogens) supporting pregnancy and preventing menstruation
(loss of the endometrial lining). Formed during the luteal
phase (secretory phase) of the menstrual cycle by proliferation of
both follicular granulosa cells (granulosa lutein cells) and thecal
cells (theca lutein cells), which together interact to
produce progesterone and oestrogens.
• Peak luteal function during the menstrual cycle, determined by
maximum luteal area, progesterone concentration and estradiol
concentration, is observed about 6 days following ovulation.
• If fertilization and pregnancy does not occur, the corpus luteum
degenerates to form the corpus albicans.
Corpus Luteum
https://www.amazon.com/Mammal-Corpus-Luteum-Microscope-Slide/dp/B003HLGG8Y

10. Corpus Albicans
• (corpora albicantia) (Latin, corpus =
body, albicans = whitish) The
histological structure formed
by luteolysis of the corpus luteum in
the ovary.
• If implantation does not occur and
the hormone hCG is not released the
corpus luteum degenerates and the
structure is white, not yellow,
because of the absence of steroid
hormone synthesis/accumulation.
https://embryology.med.unsw.edu.au/embryology/index.php/Ovary_Development#/media/File:Ovary_histology_003.jpg

11. Ovarian Hormones…
• Estrogen
• The estradiol (estrogen, oestrogen) hormone is a steroid sex hormone
expressed in female. Estrogenic activity in human placental extracts was due to
the presence of at least three compounds: estriol, estrone, and 17β-estradiol.
• In female, this hormone together with progesterone helps regulate the
menstrual cycle, controlling the growth of the uterine lining during the first
part of the cycle.
• During female development the fetal adrenal gland cortex synthesises DHEA
(and DHEA/S), an oestrogen precursor converted by the placenta into estrogen
compounds; estriol, estrone, and 17β-estradiol.
• During puberty, ovarian estrogen production is responsible for development of
the secondary feminine sex characteristics.
• In the male, Leydig cells produce estrogen into the rete testis fluid at variable
levels in different species. During male embryonic development exposure to
high levels of oestrogen can lead to genital abnormalities.
Estradiol

12. varian hormone..
The progesterone (progestin) hormone is
produced by the granulosa cells of the ovarian
ollicles at different levels during
he menstrual cycle and at high levels by the
uteal cells (P4) of the corpus luteum .
n 1934 progesterone (progestin) C21H30O2 was
irst isolated from the corpus luteum and its
structure reported by four separate groups of
esearchers.
t has a central role in reproduction, being
nvolved in ovulation, implantation, and
maintenance of pregnancy.
t prepares the uterine endometrial wall for
he implantation of embryo. Molecular structure

13. Diagrammatic Representation of Endocrine control
https://embryology.med.unsw.edu.au/embryolog
y/index.php/Menstrual_Cycle#/media/File:Menst
rual_cycle.png

14. Oocyte Development
• Primary Oocyte- arrested at early Meiosis 1
• diploid: 22 chromosome pairs + 1 pair X chromosomes (46, XX) autosomes and sex chromosome
• Oogenesis- pre-antral then antral follicle (Graafian follicle is mature antral follicle released)
• Secondary Oocyte
• 1 Day before ovulation completes (stim by LH) Meiosis 1
• haploid: 22 chromosomes + 1 X chromosome (23, X)
• nondisjunction- abnormal chromosome segregation, begins Meiosis 2 and arrests at metaphase
• note no interphase replication of DNA, only fertilization will complete Meiosis 2
https://embryology.med.unsw.edu.au/embryology/index.php/Ovary_Development

15. Follicle Factors
• External Factors
• Leutenizing Hormone (LH)
• from the anterior pituitary
• stimulate the theca interna to synthesize and secrete androgens (androstendione)
transported to granulosa cells
• granulosa cells process initially into testosterone and then by aromatase into
estrogen (estradiol)
• Follicle-stimulating hormone (FSH)
• from the anterior pituitary
• initiates follicle growth through the granulosa cells
• involved in selecting the most advanced (sensitive) follicle to proceed to
ovulation

16. • Internal Factors
• Oocyte Factors
• Growth Differentiation Factor-9 (GDF-9) - involved in the differentiation of theca cells during
this early stage of follicular development.
• Bone morphogenetic protein 15 (BMP15)
• Fibroblast growth factor 8B (FGF8B)
• Granulosal Factor(s)
• stimulates the recruitment of theca cells from cortical stromal cells
• Thecal Factor(s)
• appear to be several inhibitors of apoptotic cell death
• Epidermal growth factor (EGF)
• Transforming growth factor alpha (TGF-α)
• keratinocyte growth factor (KGF)
• hepatocyte growth factor (HGF)
• Bone morphogenetic protein 7 (BMP-7) also known as osteogenic protein-1 or OP-1
Follicle Factors….

17. Left or Right Ovulation
• In humans, it is assumed that about equal numbers of ovulations occur from each
of the ovaries.
• Whether ovulation in a succeeding cycle occurs ipsilaterally (same ovary;
right/right or left/left) and contralaterally (opposite ovary; left/right or right/left)
has also been studied.
• A shorter follicular phase length (less than 13 days) has been identified to
correlate with a greater number of contralateral ovulations, while a follicular
length greater than 14 days has a random ovulation.
• right-sided ovulation has been shown to favour pregnancy more than left-sided
ovulation
• contralateral ovulation, ovulation occurring alternately from one ovary to the other
in two consecutive cycles, has been shown to be inversely correlated with age,
greater in younger than older women.
• both ovaries appear to respond equally to clinical ovulation induction.

18. Last Menstrual Period
• The Last Menstrual Period (LMP), the menstrual period (menses) that occurs before a
pregnancy, has been widely used clinically as a date to calculate clinical pregnancy
development (gestational age). Note that in humans this is approximately two weeks
different from embryonic development, which begins at fertilisation around the mid-
point of the menstrual cycle.
• The interval between the beginning of the LMP and fertilisation can have a wide range
(7 to 25 days). This variation can be due to both maternal (menstrual cycle timing and
ovulation) and fetal (blastocyst implantation) effects. The calculation also requires an
accurate maternal recall of LMP and can be affected by irregular menses, first-
trimester vaginal bleeding, unrecognized spontaneous abortions, oral contraceptive
use.
• Measurement of fetal size by ultrasound has been used more recently to accurately
calculate pregnancy development. The ultrasound measurement tends to be more
accurate in early development staging, by the third trimester there can be some
individual variations in fetal growth. Serial ultrasound measurements may identify
these abnormal growth effects.

19. Clinical Parameters- There is a broad variability in the parameters of the adult human menstrual cycle
Clinical dimensions of menstruation and
menstrual cycle
Descriptive terms Normal limits (5th - 95th percentiles)
Frequency of menses (days) Frequent < 24
Normal 24 - 38
Infrequent > 38
Regularity of menses (days)
(cycle to cycle variation over 12 months)
Absent
Regular Variation ± 2 to 20 days
Irregular Variation greater than 20 days
Duration of flow (days) Prolonged > 8.0
Normal 4.5 - 8.0
Shortened < 4.5
Volume of monthly blood loss (ml) Heavy > 80
Normal 5 - 80
Light < 5

20. Fertility Window
• Clinical guidelines have typically identified the
"fertile window" between days 10 and 17 within
the typical 28 day menstrual cycle.
• fertile window occurred during a broad range of
days in the menstrual cycle.
• between days 6 and 21 women had at minimum a
10% probability of being in their fertile window.
• women cannot predict a sporadic late ovulation;
4 - 6% of women whose cycles had not yet
resumed were potentially fertile in the fifth week
of their cycle.
• only in about 30% of women is the fertile window
entirely within the days of the menstrual cycle
identified by clinical guidelines (between days 10
and 17)
• most women reach their fertile window earlier and
others much later.
• women should be advised that the timing of their
fertile window can be highly unpredictable, even if
their cycles are usually regular.
https://embryology.med.unsw.edu.au/embryology/index.php/Menstrual_Cycle#/media/File:Menstrual_cycle_fertility_probability_01.jpg

21. Menopause
• Menopause onset is defined clinically as the final menses, confirmed after 1
year without menstruation, about 10% of the general female population is
postmenopausal at age 45.
• A biological term describing the physiological changes that accompany the age
related loss of fertility.
• There is a decrease in ovarian follicle numbers, gradually elevated FSH levels,
onset of cycle irregularity leading to the final cessation of menses.

22. THANK YOU