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03 04 05 Female reproductive cycle, Fertilization, First week cleavage and blastocyst formation by Dr. Rabia I. Gandapore.pptx
1. Female Reproductive Cycle
Dr. Rabia Inam Gandapore
Assistant Professor
Head of Department Anatomy
(Dentistry-BKCD)
B.D.S (SBDC), M.Phil. Anatomy (KMU),
Dip. Implant (Sharjah, Bangkok, ACHERS) , CHPE
(KMU),CHR (KMU), Dip. Arts (Florence, Italy)
2. Teaching Methodology
LGF (Long Group Format)
SGF (Short Group Format)
LGD (Long Group Discussion, Interactive discussion with the use of models or diagrams)
SGD (Short Group)
SDL (Self-Directed Learning)
DSL (Directed-Self Learning)
PBL (Problem- Based Learning)
Online Teaching Method
Role Play
Demonstrations
Laboratory
Museum
Library (Computed Assisted Learning or E-Learning)
Assignments
Video tutorial method
3. Goal/Aim (main objective)
To help/facilitate/augment the students about the:
Describe the ovarian cycle.
Discuss the process of follicular development.
Explain the process of ovulation.
Correlate with the phases of menstrual cycle
Define fertilization.
Describe the process of fertilization.
Describe the outcome of fertilization
Describe the process of cleavage of zygote
Discuss the formation of blastocyst.
Summarize the events of first week of development normal and abnormal
4. Specific Learning Objectives (cognitive)
At the end of the lecture the student will able to:
Enumerate Menstrual cyclic phases
Sketch labeled diagram of the different stages of first week of development
5. Psychomotor Objective: (Guided response)
A student to draw labelled diagram of different stages of first week of development
6. Affective domain
To be able to display a good code of conduct and moral values in the class.
To cooperate with the teacher and in groups with the colleagues.
To demonstrate a responsible behavior in the class and be punctual, regular, attentive and
on time in the class.
To be able to perform well in the class under the guidance and supervision of the teacher.
Study the topic before entering the class.
Discuss among colleagues the topic under discussion in SGDs.
Participate in group activities and museum classes and follow the rules.
Volunteer to participate in psychomotor activities.
Listen to the teacher's instructions carefully and follow the guidelines.
Ask questions in the class by raising hand and avoid creating a disturbance.
To be able to submit all assignments on time and get your sketch logbooks checked.
7. Lesson contents
Clinical chair side question: Students will be asked if they know what is the function of
Outline:
Activity 1 The facilitator will explain the student's first week of development
Activity 2 The facilitator will ask the students to make a labeled diagram of the first week of
development stages
Activity 3 The facilitator will ask the students a few Multiple Choice Questions related to it with
flashcards.
8. Students assessment: MCQs, Flashcards, Diagrams labeling.
Learning resources: Langman’s T.W. Sadler, Laiq Hussain Siddiqui, Snell Clinical Anatomy, Netter’s
Atlas, BD Chaurasia’s Human anatomy, Internet sources links.
9. First week of Development:
Ovulation to Implantation
OVARIAN CYCLE
OVULATION
PHASES OF MENSTRUAL CYCLE
10. Objectives
Describe the ovarian cycle.
Discuss the process of follicular development.
Explain the process of ovulation.
Correlate with the phases of menstrual cycle
11. Ovarian Cycle
At puberty: female begins to undergo regular monthly cycles.
These sexual cycles are controlled by hypothalamus.
Gonadotropin-releasing hormone (GnRH) produced by hypothalamus acts on
cells of anterior pituitary gland that secrete gonadotropins.
These hormones, follicle-stimulating hormone (FSH) and luteinizing hormone
(LH), stimulate & control cyclic changes in ovary.
12. At beginning of each ovarian cycle: 15 to 20 primary (preantral) stage follicles
are stimulated to grow under influence of FSH (without it, these primary follicles die
and become atretic.)
FSH rescues 15 to 20 of these cells from a pool of continuously forming primary
follicles.
Under normal conditions: only one of these follicles reaches full maturity, and
only one oocyte is discharged; the others degenerate and become atretic.
In next cycle: another group of primary follicles is recruited, and again, only one
follicle reaches maturity.
Most follicles degenerate without ever reaching full maturity.
When a follicle becomes atretic: oocyte & surrounding follicular cells degenerate
and are replaced by connective tissue, forming a corpus atreticum.
13.
14. FSH also stimulates maturation of follicular (granulosa) cells surrounding the
oocyte.
Proliferation of these cells is mediated by growth differentiation factor-9 (GDF-9),
a member of transforming growth factor-β (TGF-β) family.
In cooperation, granulosa & thecal cells produce estrogens that:
(a) cause uterine endometrium to enter the follicular or proliferative phase
(b) cause thinning of cervical mucus to allow passage of sperm
(c) stimulate pituitary gland to secrete LH.
At mid-cycle, there is an LH surge that
1. elevates conc. of maturation-promoting factor, causing oocytes to complete
meiosis I & initiate meiosis II
2. stimulates production of progesterone by follicular stromal cells (luteinization)
causes follicular rupture & ovulation.
15.
16.
17.
18.
19. OVULATION
Days immediately preceding ovulation, under influence of FSH & LH, secondary follicle grows rapidly to a
diameter of 25 mm.
Final development of secondary follicle: there is an abrupt increase in LH that causes the primary oocyte to
complete meiosis I & follicle to enter the pre-ovulatory stage.
Meiosis II is also initiated, but oocyte is arrested in metaphase approximately 3 hours before ovulation.
Surface of ovary begins to bulge locally, & at apex, an avascular spot, the stigma, appears.
High conc. of LH increases collagenase activity, resulting in digestion of collagen fibers surrounding follicle.
Prostaglandin levels increase in response to LH surge & cause local muscular contractions in ovarian wall.
Contractions extrude the oocyte, which together with its surrounding granulosa cells from the region of
cumulus oophorus, breaks free (ovulation) & floats out of ovary.
Some of cumulus oophorus cells then rearrange themselves around zona pellucida to form corona radiate.
20.
21.
22.
23. CORPUS LUTEUM
After ovulation, granulosa cells remaining in wall of ruptured
follicle, together with cells from theca interna, are vascularized
by surrounding vessels.
Under the influence of LH, these cells develop a yellowish
pigment & change into lutean cells, which form corpus luteum
& secrete hormone progesterone.
Progesterone, together with estrogenic hormones, causes
uterine mucosa to enter the progestational or secretory stage
in preparation for implantation of embryo.
24.
25. OOCYTE TRANSPORT
Shortly before ovulation, fimbriae of the oviduct begin to sweep over surface
of ovary, & the tube itself begins to contract rhythmically.
Oocyte surrounded by some granulosa cells is carried into the tube by these
sweeping movements of fimbriae & by motion of cilia on epithelial lining.
Once in tube, cumulus cells withdraw their cytoplasmic processes from zona
pellucida & lose contact with oocyte.
Once the oocyte is in the uterine tube, it is propelled by cilia with the rate of
transport regulated by the endocrine status during and after ovulation.
In humans, fertilized oocyte reaches uterine lumen in approx. 3 to 4 days.
26.
27. CORPUS ALBICANS
If fertilization does not occur, corpus luteum reaches maximum development approx. 9 days after
ovulation.
It can easily be recognized as a yellowish projection on surface of ovary.
corpus luteum shrinks because of degeneration of lutean cells & forms a mass of fibrotic scar tissue, the
corpus albicans.
Progesterone production decreases, precipitating menstrual bleeding.
If oocyte is fertilized, degeneration of corpus luteum is prevented by human chorionic gonadotropin
(hCG), a hormone secreted by syncytiotrophoblast of the developing embryo.
Corpus luteum continues to grow & forms corpus luteum of pregnancy (corpus luteum graviditatis).
By end of third month, this structure may be 1/3 to 1/2 of total size of ovary.
Yellowish luteal cells continue to secrete progesterone until end of 4th month; they regress slowly as
secretion of progesterone by trophoblastic component of placenta becomes adequate for maintenance of
pregnancy.
Removal of corpus luteum of pregnancy before 4th month usually leads to abortion.
31. FERTILIZATION
Male & female gametes fuse (Occurs in
ampullary region i.e. widest part of
uterine tube-Close to ovary)
form 1st cell (single & diploid)
Only 1 % of sperm deposited in vagina
enter cervix
Spermatozoa may remain viable in the
female reproductive tract for several days
32.
33.
34. Movement of sperm from cervix to uterine tube
(Oviduct)
Movement of sperms takes 2-7 hours from cervix to oviduct
Accomplished by
flagellar activity of sperms (propulsion)
Fluid created by Uterine cilia and
Muscular contractions of uterus and uterine tubes
Reaching isthmus: sperm becomes less motile (isthmus is
sperm reservoir) & stops migration
At ovulation: sperm again becomes motile, perhaps because of
chemoattractants produced by cumulus cells surrounding the egg,
swim to ampulla where fertilization usually occurs
35.
36. Processes prior to fertilization by spermatozoa
Spermatozoa are not able to fertilize oocyte immediately
upon arrival in female genital tract but must undergo
(a) Capacitation
(b) Acrosome reaction
37. a. Capacitation
Period of conditioning in fallopian tube (last 7 hrs)
Epithelial interactions between sperm & mucosal
surface of uterine tube
Glycoprotein coat & seminal plasma proteins are
removed from plasma membrane overlying
acrosomal region of spermatozoa
Only capacitated sperm can pass through corona
cells & undergo acrosome reaction
38.
39.
40. b. Acrosome reaction
Occurs after binding to zona pellucida
Induced by Zona proteins
Release of enzymes occur: needed to
penetrate the zona pellucida,
1. Acrosin Enzyme
2. Trypsin-like-substances Enzyme
41. PHASES OF FERTILIZATION
Phase 1: Penetration of corona radiata
Phase 2: Penetration of zona pellucida
Phase 3: Fusion of oocyte & sperm cell
membranes
42. PHASE 1: PENETRATION OF CORONA RADIATA
200 to 300 million spermatozoa
deposited in female Genital tract, only 300
to 500 reach the site of fertilization.
Only one of these fertilizes the egg.
(others aid the fertilizing sperm in
penetrating the barriers protecting the
female gamete).
Capacitated sperm passes freely
through corona cells
43. PHASE 2: PENETRATION OF ZONA PELLUCIDA
Zona is a glycoprotein shell surrounding the egg that facilitates
& maintains sperm binding & induces acrosome reaction
(ligand ZP3-zona protein)
Penetration of Zona is facilitated by release of acrosomal
enzymes (acrosin), thereby coming in contact with the plasma
membrane of oocyte
Permeability of zona pellucida changes when the head of the
sperm comes in contact with the oocyte surface. This contact
results in release of lysosomal enzymes from cortical granules
lining the plasma membrane of the oocyte
In turn, these enzymes alter properties of zona pellucida (zona
reaction) to prevent more sperm penetration
44.
45.
46. PHASE 3: FUSION OF THE OOCYTE
AND SPERM CELL MEMBRANES
After adhesion: plasma membranes of sperm & egg
fuse
Because the plasma membrane covering the
acrosomal head cap disappears during the
capacitation, actual fusion is accomplished
between the oocyte membrane and the membrane
that covers the posterior region of the sperm head
In human: both head & tail of spermatozoon enter
the cytoplasm of oocyte, but the plasma membrane
is left behind on oocyte surface.
47. Egg response after spermatozoon entered Oocyte
1. Cortical & zona reactions: As a result of release of cortical oocyte granules, which contain
lysosomal enzymes,
(a) oocyte membrane becomes impenetrable to other spermatozoa
(b) zona pellucida alters its structure & composition to prevent sperm binding & penetration.
These reactions prevent polyspermy(penetration of more than one spermatozoon into oocyte)
2. Resumption of second meiotic division: Oocyte finishes its second meiotic division
immediately after entry of spermatozoon. Second Polar body & Definitive Oocyte; Its
chromosomes (22+X) arrange themselves in a vesicular nucleus known as female pronucleus
3. Metabolic activation of egg: encompass initial cellular & molecular events associated with
early embryogenesis.
48. Spermatozoon moves forward until it lies close
to female pronucleus. Its nucleus becomes
swollen & forms male pronucleus ; tail
detaches & degenerates.
Eventually, the two pronuclei come into close
contact & lose their nuclear envelopes
49. During growth of male & female pronuclei (both
haploid), each pronucleus must replicate its DNA.
Immediately after DNA synthesis, chromosomes
organize on the spindle in preparation for a normal
mitotic division.
23 maternal & 23 paternal (double) chromosomes
split longitudinally at centromere,
Sister chromatids move to opposite poles, providing
each cell of zygote with normal 2n of chromosomes &
DNA
Deep furrow appears on surface of cell, gradually
dividing cytoplasm into 2 parts
50. OUTCOME OF FERTILIZATION
Restoration of diploid number of chromosomes
half from father & half from mother
Zygote contains a new combination of chromosomes different from both parents
Determination of sex of new individual
X-carrying sperm produces a female (XX) embryo,
Y-carrying sperm produces a male (XY) embryo
Initiation of cleavage
Without fertilization, oocyte usually degenerates 24 hours after ovulation
52. First week of Development
CLEAVAGE
BLASTOCYST FORMATION
IMPLANTATION
53. Objectives
Describe the process of cleavage of zygote
Discuss the formation of blastocyst.
Summarize the events of first week of
development normal and abnormal
54. CLEAVAGE
Zygote reached 2 cell stage
Undergoes series of mitotic divisions,
Cells become smaller with each
cleavage division, These cells are
known as blastomeres.
30HRS 40 HRS 4 DAYS
55. Loose arrangement & compaction
Until 8 cell stage, they form a
loosely arranged clump.
COMPACTION:
However, after 3rd cleavage,
blastomeres maximize their contact
with each other, forming a compact
ball of cells held together by tight
junctions.
56. Compaction process, segregates
inner cells, from outer cells.
Approx. 3 days after fertilization,
cells of compacted embryo divide
again to form a 16-cell morula
(mulberry).
Still surrounded by zona
Pellucida which disappears at end
of 4th day
57. Inner cells of morula= Inner cell
mass give rise to tissues of embryo
proper
Surrounding cells of morula= outer
cell mass forms Trophoblast, (which
later contributes to placenta
58. Blastocyst formation-32 cell stage
When morula enters uterine
cavity, fluid begins to penetrate
through zona pellucida into
intercellular spaces of inner cell
mass.
Gradually intercellular spaces
become confluent & finally a
single cavity, blastocele, forms
& embryo is a blastocyst.
59.
60. Cells of inner cell mass, now
called embryoblast, are at one
pole,
Outer cell mass, or trophoblast,
flatten & form epithelial wall of
blastocyst.
Zona pellucida has
disappeared (at late blastocyst
stage), allowing implantation to
begin.
61.
62. Penetration of trophoblastic cells
Trophoblastic cells over embryoblast pole begin
to penetrate between epithelial cells of uterine
mucosa about 6th day.
63. Penetration of trophoblastic cells
(cont’d)
Implantation is
result of mutual
trophoblastic &
endometrial action.
64. By the end of first week...
Human zygote
has passed through morula & blastocyst stages
Has begun implantation in uterine mucosa.
66. Wall of uterus
Consists of 3 layers:
(a) Endometrium or mucosa:
Lining inside wall
(b) Myometrium: thick layer of
smooth muscle
(c) Perimetrium: peritoneal
covering lining outside wall
67. Menstrual cycle
From puberty (11–13 years) until menopause
(45–50 yrs),
Endometrium undergoes changes in a cycle
of approx. 28 days under hormonal control by
Ovary
Uterine endometrium: passes via 3 stages
of menstrual cycle:
Follicular or proliferative phase
Secretory or progestational phase
Menstrual phase
68.
69. Changes in endometrium & corresponding changes in ovary during a regular menstrual
cycle without fertilization
70. Menstrual cycle (cont’d)
Proliferative phase
begins at end of menstrual phase,
is under influence of estrogen
parallels growth of ovarian follicles.
Secretory phase
begins approximately 2 to 3 days after ovulation
in response to progesterone produced by corpus luteum.
71.
72. Uterus at time of implantaion
At time of implantation, mucosa of
uterus is in secretory phase, during
which time:
Uterine glands & arteries become
coiled
Tissue becomes succulent.
73. Three distinct layers of endometrium
3 distinct layers recognized in
endometrium:
Superficial: compact layer
Intermediate: spongy layer
Thin: basal layer
74. Implantation of blastocyst
In endometrium along the
anterior or posterior wall of
body of uterus (Becomes
embedded between
openings of glands)
75. If oocyte is “”NOT”” fertilized
Venules & sinusoidal spaces gradually become packed
with blood cells & extensive diapedesis of blood into
tissue is seen.
When menstrual phase begins, blood escapes from
superficial arteries & small pieces of stroma & glands break
away.
During the following 3 or 4 days, compact & spongy
layers are expelled from uterus
Basal layer is only part of endometrium that is retained
Basal layer, supplied by its own arteries,basal arteries,
functions as regenerative layer in proliferative phase
rebuilding of glands & arteries
78. Normal Week of Embryonic Development
Fertilization: week begins with fusion of sperm & egg forming a single-celled zygote.
Cleavage: zygote undergoes several rounds of cell division, known as cleavage,
producing a multicellular structure called a blastocyst.
Blastocyst Formation: By end of week, blastocyst forms, consisting of an outer cell
layer (trophoblast) & inner cell mass.
Implantation: blastocyst moves into uterus & attaches to uterine lining
Formation of the Bilaminar Embryonic Disc: Inner cell mass differentiates into 2
layers, forming bilaminar embryonic disc consisting of epiblast & hypoblast.
79. Abnormal Week of Embryonic Development
Fertilization Issues: Abnormalities in fertilization, such as polyspermy (multiple
sperm fertilizing one egg), can lead to genetic & developmental anomalies.
Cleavage Abnormalities: Problems during cleavage can result in uneven cell
distribution, leading to issues in development of blastocyst.
Blastocyst Defects: Abnormalities in blastocyst formation may impact the proper
differentiation of cells, affecting subsequent stages of development.
Implantation Failure: If blastocyst fails to implant correctly into uterine lining, it can
result in unsuccessful pregnancy.
Genetic Aberrations: Mutations or chromosomal abnormalities during early cell
divisions can lead to genetic disorders affecting developing embryo.
There are two kinds of corpus luteum, one is formed inside the vesicular follicle after ovulation, the other is formed outside the follicle without ovulation. The former is the true corpus luteum and the latter is the accessory corpus luteum or corpus atreticum.