MENSTRUAL

CYCLE,
FERTILIZATION,
EMBRYOGENESIS
BACAY | CALACDAY | GANANCIAS | MASAGCA
SEP 4, 2020
MENSTRUAL
CYCLE,
The menstrual cycle often begins at puberty
between the ages of 8 and 15 (average age of 12). It
usually starts two years after breasts and pubic
hair start to develop.

Menopause- average age of 51.5 years old

( Philippines: 48 years old). Signs and symptoms
may occur 3-5 years before
Predictable, regular, cyclical, and spontaneous ovulatory
menstrual cycles are regulated by complex interactions of the
hypothalamic-pituitary-ovarian axis. Key players are the
following:

• Pituitary-derived gonadotrophins
o Follicle-stimulating hormone(FSH)
o Luteinizing hormone(LH)

• Ovarian sex steroid hormones

o Estrogen
o Progesterone
The follicular phase (days 1 to 14) is characterized by
rising estrogen levels, endometrial thickening, and
selection of the dominant “ovulatory” follicle.

During the luteal phase (days 14 to 21), the corpus

luteum (CL) produces estrogen and progesterone, which
prepare the endometrium for implantation. If
implantation occurs, the developing blastocyst begins to
produce human chorionic gonadotropin (hCG) and
rescues the corpus luteum, thus maintaining
progesterone production.
The average cycle duration approximates 28 days but
ranges from 25 to 32 days
Two-gonadotropin principle of ovarian steroid
hormone production.
Luteinizing
hormone (LH) controls theca
cell production of
androstenedione

Follicular stimulating
hormone(FSH) controls
granulosa cell capacity to
convert androstenedione to
estradiol
After ovulation,
corpus luteum forms and
both theca-lutein and granulosa-
lutein cells respond to LH

Theca-lutein cells continue to

produce androstenedione

Granulosa-lutein cells greatly

increase their capacity to produce
progesterone and to convert
androstenedione to estradiol.
Low-density
lipoproteins (LDL) are
an important source of
cholesterol for
steroidogenesis.

If pregnancy occurs,
human chorionic
gonadotropin (hCG)
rescues the
corpus luteum through
their shared LH-hCG
receptor
After the appearance of LH receptors, the preovulatory granulosa
cells begin to secrete small quantities of progesterone.

Its secretion is believed to exert positive feedback on the estrogen-

primed pituitary to either cause or augment LH release.

During the early follicular phase, granulosa cells also produce inhibin
B, which can feed back on the pituitary to inhibit FSH release.

During the late follicular phase, LH stimulates thecal cell production of

androgens, particularly androstenedione, which are then transferred to
the adjacent follicles where they are aromatized to estradiol.
As the dominant follicle begins to grow, estradiol and inhibin
production rises and results in a decline of follicular phase
FSH. This drop in FSH levels is responsible for the failure of other
follicles to reach preovulatory status—the Graafian follicle stage—
during any one cycle.

Thus, 95 percent of plasma estradiol produced at this time is

secreted by the dominant follicle—the one destined to ovulate.
Concurrently, the contralateral ovary is relatively inactive.
Proliferative/Follicular phase (Day 1 - 14)

• Proliferative/Proliferative
phase: length varies from 10 -
20 days, "ideal" is 14 days;
during this phase, glands
become more tortuous due to
epithelial proliferation, in
response to estrogen
production and estrogen
receptors on epithelium
Proliferative/Follicular
phase (Day 1 - 14)
 • thin surface
Early epithelium, straight short
glands, compact stroma,
proliferative minimal mitotic activity and
large nuclei
(days 4 - 7):
 Mid proliferative
(days 8 - 10)

• columnar surface epithelium; longer curving

glands, variable stromal edema and
numerous mitotic figures
Late proliferative
(days 11 - 14):

• undulant surface epithelium, tortuous

glands with prominent mitotic activity
and pseudostratification; dense
stroma, subnuclear vacuoles in less
than 50% of glands
Proliferative/Follicular
phase (Day 1 - 14)
 Ovulation
• The onset of the gonadotropin
surge resulting from increasing
estrogen secretion by preovulatory
follicles is a relatively precise
predictor of ovulation. It occurs 34
to 36 hours before ovum release
from the follicle. LH secretion
peaks 10 to 12 hours before
ovulation and stimulates
resumption of meiosis in the ovum
and release of the first polar body
 • Ovulation occurs approximately 10-12 hours after the LH peak. There is also
Ovulation a sudden switch from a negative to positive feedback
Secretory/Luteal
Phase
Early Secretory
Endometrium: (Day 15-20)
• Traditionally assumed to be 14 days, but may
vary. Progesterone secretion inhibits
endometrial proliferative activity and induces
secretory activity
• Day 15: no changes from late proliferative;
also known as interval endometrium;
presence of scattered nuclear vacuoles is
NOT specific for ovulation (must be 50% or
more)
• Days 16 - 20: "piano key" appearance;
subnuclear vacuoles (day 16), vacuoles at
level of nuclei (day 17)
Late Secretory
Endometrium (day 21-28)
• Day 22: maximal stromal edema in luteal phase; best
time for implantation
• Day 23: prominent spiral arterioles (thickened walls,
coiling and endothelial proliferation)
• Day 24: perivascular predecidualization (stromal cell
hypertrophy with accumulation of cytoplasmic
eosinophilia); serrated / tortuous glands
• Day 26: confluence of predecidual tissue; stromal
granulocytes (probably lymphocytes) appear
• Day 27: prominent stromal granulocytes; focal necrosis and
hemorrhage
• Day 28: shedding, also called glandular and stromal
breakdown; prominent necrosis and hemorrhage; predecidual
stroma and glandular exhaustion; nuclear dust at base of
glandular epithelium; condensed stroma with overlying
papillary-syncytial change; intravascular fibrin thrombi; stromal
granulocytes
Menstruation Phase
(day 28)
• In the absence of a pregnancy, steroid
hormone levels begin to fall due to
declining corpus luteum function.
Progesterone withdrawal results in
increased coiling and constriction of the
spiral arterioles. This eventually results in
tissue ischemia due to decreased blood
flow to the superficial endometrial
layers, the spongiosa and compacta. The
endometrium releases prostaglandins
that cause contractions of the uterine
smooth muscle and sloughing of the
degraded endometrial tissue.
FERTILIZATION
 ◦ The primordial germ cells in both males and females are large
eosinophilic cells derived from endoderm in the wall of the yolk sac.
OOCYTE & ◦ Oogenesis begins with the replication of the diploid oogonia through
mitosis to produce primary oocytes at 18-22 weeks of gestation
MEIOSIS ◦ Through apoptosis the numbers decline at menarche.

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◦ There is a large variance among
individuals and a direct correlation
between the number of fetal oocytes
and the age of menopause.
◦ Accelerated apoptosis is seen in Turner
syndrome resulting in few oocytes at birth

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 ◦ Begins at 10-12 weeks’ gestation
◦ Mechanism by which diploid organisms
MEIOSIS reduce their gametes to a haploid state so
that they can recombine again during
fertilization to become diploid organisms

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 ◦ With ovulation, the secondary oocyte
and adhered cells of the cumulus—
oocyte complex are freed from the
FERTILIZATION ovary.
◦ Normally occurs in the oviduct, must
take within a few hours and no more
than a day after ovulation

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 ◦ Almost all pregnancies result when
intercourse occurs during the 2 days
preceding or on the day of ovulation.
FERTILIZATION
◦ Fusion of the two nuclei and
intermingling of maternal and paternal
chromosomes creates the zygote

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 ◦ Involves the processes of
◦ Capacitation
FERTILIZATION ◦ Chemotaxis
◦ Hyperactivated Motility
◦ Acrosome reaction

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 ◦ Capacitation - to allow localization of protein
complexes in the head of the sperm, which will
subsequently bind the ZP
◦ Chemotaxis
◦ Hyperactived motility - involves increased
FERTILIZATION vigorous movement of the sperm in order to
penetrate the cumulus (granulosa) cells
surrounding the oocyte and is most likely due to
progesterone.
◦ Acrosome reaction - acrosin release to locally
degrade the zona pellucida

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 ◦ As many sperm may initially bind
the ZP, a mechanism must be in
FERTILIZATION place to prevent fertilization by
more than one sperm
(polyspermia).

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 ◦ The majority of a single sperm enters the oocyte.
◦ Only the centrioles and the nucleus survive, whereas
mitochondria in the midpiece and tail are destroyed.
◦ The sperm centrioles interact with α-tubulin from the
oocyte to form a microtubule network for migration
FERTILIZATION of pronuclei and subsequent separation of
chromosomes during the first mitosis

◦ Thus mitochondria are of maternal origin, whereas

centrioles are paternal.

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 A significant number of fertilized oocytes do not complete
cleavage:
◦ failure of appropriate chromosome arrangement on the
spindle
◦ specific gene defects that prevent the formation of the
spindle
◦ environmental factors
FERTILIZATION
Teratogens acting at this point are usually either completely
destructive or cause little or no effect.

Twinning may occur by the separation of the two cells

produced by cleavage, each of which has the potential to
develop into a separate embryo
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◦ Early human development is described
by days or weeks postfertilization –
postconceptional
◦ 1 week postfertilization corresponds to
approximately 3 weeks from the LMP in
women with regular 28-day cycles

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 ◦ After fertilization, the zygote
undergoes rapid mitotic division
to reach the next stage of
MORULA & approximately 16 cells called a
morula
BLASTULA ◦ After 4 to 5 days traversing the
fallopian tube, the embryo arrives
into the uterine cavity at the blast
stage
◦

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◦ The zygote – a diploid cell with 46
chromosomes – undergoes cleavage,
and cells produced by this division are
called blastomeres

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 ◦ a solid mulberry-like ball of cells
◦ enters the uterine cavity approximately 3 days
after fertilization
MORULA ◦ Gradual accumulation of fluid between the
morula cells leads to the formation of the early
blastocyst.

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 ◦ As early as 4 to 5 days after fertilization,
the 58-cell blastula differentiates into 5
embryo-producing cells – inner cell
BLASTOCYST mass
◦ Trophectoderm – remaining 53 outer
cells
◦ Destined to form trophoblasts

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 ◦ 6 or 7 days after fertilization, the
blastocyst implants into the uterine
IMPLANTATION wall.

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 APPOSITION ADHESION/ INVASION
Initial contact of the ATTACHMENT Penetration and
blastocyst to the Increased physical invasion of
uterine wall contact between the syncytiotrophoblast
blastocyst and decidua and cytotrophoblasts
into the decidua,
inner third of the
myometrium and
3 PHASES uterine vasculature

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Stage 1: Zygote

Stage 2: Morula

Stage 3:
Free/Unattached
blastocyst

Stage 4:
Implantation
 ◦ Human placental formation begins with
Trophoblast the trophectoderm, which gives rise to
a trophoblast cell layer encircling the
Development blastocyst

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◦ Their invasiveness promotes
implantation
◦ Has nutritional role for the conceptus
◦ Endocrine function: essential to
maternal physiological adaptations & to
pregnancy maintenance

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◦ By the 8th postfertilization (after implantation)
, trophoblasts have differentiated into an
outer multinucleated syncytium – primitive
syncytiotrophoblast and inner layer of
primitive mononuclear cells -
cytotrophoblasts

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◦ After implantation is complete,
trophoblasts further differentiate along
two main pathways giving rise to:
◦ Villous
◦ Extravillous trophoblasts

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 VILLOUS TROPHOBLASTS
◦ Generate chorionic villi
◦ Primarily transport oxygen,
nutrients, and other
compounds between the fetus
and the mother.

EXTRAVILLOUS
TROPHOBLASTS
◦ Migrate into the decidua and
myometrium
◦ Classification:
◦ Interstitial trophoblast
◦ Endovascular
trophoblasts

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 ◦ At 9 days of development, the
Early blastocyst wall facing the uterine lumen
is a single layer of flattened cells.
Invasion ◦ By the 10th day, the blastocysts totally
encased within endometrium

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◦ As early as 7 ½ days postfertilization,
the inner cell mass or embryonic disc
differentiates into a thick plate of
primitive ectoderm and an underlying
layer of endoderm

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◦ Chorion
◦ Composed of trophoblasts and
mesenchyme
◦ Some mesenchymal cells will condense
to form the body stalk.
◦ Stalk will join the embryo to the
nutrient chorion and later develops into
the umbilical cord

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◦ Beginning approximately 12 days after
conception, the syncytiotrophoblast is
permeated by a system of
intercommunicating channels –
trophoblastic lacunae

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EMBRYOGENESIS
Early human embryos. Ovulation ages: A. 19 days (presomite). B. 21 days (7 somites). C. 22 days (17
somites)
Drawing of an 18-day embryo shows the amnionic cavity and its relations to chorion and yolk sac
Three- to four-week-old embryos.

A, B. Dorsal views of embryos during

22 to 23 days of development showing
8 and 12 somites, respectively.

C–E. Lateral views of embryos during

24 to 28 days, showing 16, 27, and 33
somites, respectively.
Embryo photographs. A. Dorsal view of an embryo at 24 to 26 days B. Lateral view of an embryo at
28 days. C. Lateral view of embryo-fetus at 56 days, which marks the end of the embryonic period
and the beginning of the fetal period. The liver is within the fine, white circle.
A. This is an image of a 6-
week and 4-day embryo.
It depicts measurement
of the crown-rump
length, which is 7.4mm at
this gestational age

B. Despite the early

gestational age, M-mode
imaging readily
demonstrates embryonic
cardiac activity. The heart
rate in this image is 124
beats per minute
 ◦ Cunningham & et. al. (2018). Williams
Obstetrics. 25th ed. US: McGraw-Hill
REFERENCES Education
◦ Lobo & et. al. (2017). Comprehensive
Gynecology. 7th ed. US: Elsevier
THANK YOU!

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