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July 25, 2016

PHYSIOLOGY OF MENSTRUATION AND DECIDUA

PDr. Cherry G. Ilarde
Department of Obstetrics

TOPIC OUTLINE

I. Menstrual Cycle
II. Predominant hormones
a. Gonadotropin-releasing hormone (GnRH)
b. Follicle-stimulating hormone (FSH)
c. Luteinizing hormone (LH)
d. Estrogen
e. Progesterone
f. Enkephalinase
III. Phases of Menstrual Cycle
IV. Ovarian Cycle
a. Follicular phase
b. Ovulation
c. Luteal phase
d. Pre-menstrual phase
V. Endometrial Cycle
a. Proliferative
b. Secretory
c. Menstrual
d. Anatomic events during menstruation Figure 1. Hormones’ interplay during menstruation and
VI. Menstruation implantation
a. Prostaglandins
VII. Endometrium
a. Endometrial dating
b. Cervical gland secretions
VIII. Decidua
a. Formation of the deciduas
b. Decidual parts based on location
c. Decidual reaction
d. Decidual blood supply
e. Decidual histology
f. Decidual prolactins
IX. Implantation and early trophoblast formation
a. Fertilization and implantation
b. Blastocyst implantation

MENSTRUAL CYCLE

 Also called the ovarian-endometrial cycle

 Predictable, regular, cyclical, and spontaneous ovulatory
menstrual cycle
 Regulated by the hypothalamic-pituitary axis, ovaries, and
genital tract
 Ideally, 28 days with range of 25-35 days
 Endometrial shedding with hemorrhage that is dependent
on sex steroid hormone-directed changes in the blood flow
in the spiral arteries
Figure 2. Hypothalamic-pituitary-gonadal axis

PREDOMINANT HORMONES
GONADOTROPIN-RELEASING HORMONE (GnRH)
 Secreted from hypothalamus in a pulsatile maner
throughout the menstrual cycle
 GnRH FSH and LH (from adenohypophysis or anterior
pituitary)  estrogen and progesterone (in ovary)
 LH >GnRH in terms of sensitivity to changes in GnRH

From Doc Ilarde’s Lecture (2016):

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 There is a rapid and undiluted transport of neurohormones
to the pituitary gland
 Major route =cyclic, alternate route = tonic
 Anterior hypothalamus  Basal hypothalamus (arcuate
nucleus)  via tubulo-infundibular tract  Median
eminence (infundibulum) Hypophyseal plexus
anterior pituitary
 Kallman syndrome:
o Failure of hypothalamus to release GnRH at appropriate
time
o A form of hypogonadotropichypogonadism (HH)
o Accompanied by anosmia (lack of sense of smell)
Figure 3. Production and transport of GnRH
Early Follicular Phase:
 Ave. Frequency of GnRH secretion = 1/90mins
 Increases to 1/60-70mins
Luteal Phase:
 Decreases with increase in amplitude
FOLLICLE-STIMULATING HORMONE (FSH)
From Doc Ilarde’s Lecture (2016):
 From the adenohypophysis, gonadotropes (specialized cells
that produce gonadotropins) release FSH and LH.
 FSH:
o Heterodimer consisting of 2 polypeptide units
o Similar α subunit with HCG and TSH
o β subunit – confers its specific biologic action
o Initiates follicular growth by affecting granulosa cells
From 2B 2018 Trans:
 Secretion is highest & most critical during the 1st week of
the follicular stage
 Induces estrogen & progesterone by activating aromatase
and P450 enzymes
 Exerts negative feedback on GnRH secretion
 Induce proliferation of granulosa cells and expression of LH
receptors on granulosa cells
LUTEINIZING HORMONE (LH)
 Responded to by theca and luteal cells
 From anterior pituitary
 For growth of preovulatory follicles and luteinization and
ovulation of dominant follicle
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 Also a heterodimeric glycoprotein with α subunit similar to
HCG and TSH
Follicular Phase:
 Induce androgen synthesis by theca cells
 Stimulates proliferation, differentiation & secretion of
follicular thecal cells and increases LH receptors on
granulosa cells
Preovulatory LH Surge:
 Drives oocyte into 1st meiotic division and initiates
luteinization of thecal and granulosa cells
 Resulting corpus luteum produce high levels of progesterone
and some estrogen
 C. luteum production = increase progesterone
 LH surge – triggers ovulation
ESTROGEN
From 2B 2018 Trans:
 Secreted by the granulosa cells of the dominant ovarian
follicle
 For developement of antrum& maturation of the graafian
follicle
 Predominant at the end of the follicular phase directly
preceding ovulation
 2 receptors: estrogen receptor  and 
Accdg. toWilliams (2014):
 The most biologically potent naturally occurring estrogen—
17β-estradiol—is also secreted by luteinized granulosa cells
of the corpus luteum.
 Estrogens function in many cell types to regulate follicular
development, uterine receptivity, or blood flow.
 After ovulation, estrogen levels decrease followed by a
secondary rise that reaches a peak production of 0.25
mg/day of 17β-estradiol at the midluteal phase. Toward the
end of the luteal phase, there is a secondary decline in
estradiol production.
Figure 4. Ovarian steroid hormone production
Accdg to Williams (2014):
 During the follicular phase (left), LH controls theca cell
production of androstenedione (androgen).
 Androstenedione diffuses to granulosa cells and acts as
precursor to estradiol production.
 The granulosa cell capacity to convert androstenedione to
estradiol is controlled by FSH.
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 After ovulation (right), the corpus luteum forms and both
the theca-lutein and granulosa-lutein cells respond to LH.
 After the appearance of LH receptors, the preovulatory
granulosa cells begin to secrete small quantities of
progesterone.
 In addition, during the early follicular phase, granulosa cells
also produce inhibin B, which can feed back on the pituitary
to inhibit FSH release. As the dominant follicle begins to
grow, production of estradiol and the inhibins increases and
results in a decline of follicular-phase FSH. This contributes
to the failure of other follicles to reach pre-ovulatory status.
 The theca-lutein cells continue to produce androstenedione
while,
 The granulosa-lutein cells greatly increase their capacity to
produce progesterone, and to convert androstenedione to
estradiol.
 Low-density lipoprotein (LDL) is an important source of
cholesterol for steroidogenesis.
PROGESTERONE
Accdg. to 2B 2018 Trans:
 Secreted at level of ovary primarily by luteinized follicles
 Secreted by granulosa cells and corpus luteum
 Levels just prior to ovulation
 Peak :5-7 days post ovulation
 Require p450
 Circulating forms:
o progesterone
o 17-hydroxyprogesterone
 Stimulate the release of proteolytic enzymes from
thecal cells
 Induce migration of blood vessel into follicle wall
 Stimulate prostaglandin secretion in follicular tissues
 Receptors:
o PR-A : inhibit PR-B gene regulation and expressed in
the whole cycle
o PR-B : expressed only up to midluteal phase
Accdg. to Doc Ilarde (2016 lecture):
 Progesterone is secreted at midluteal phase (25 to
50mg/day).
 It is the hallmark of the luteal phase.
 May come from LDLs (low-density lipoprotein) -> luteinized
follicles -> progesterone production
 Luteal progesterone production decreases, it signals the
start of menstruation
 With pregnancy, the corpus luteum continues to secrete
progesterone
ENKEPHALINASE
 In endometrial stromal cells
 Degrades endothelins (potent vasoconstrictor)
 Activity in parallel with blood levels of progesterone after
ovulation
 Highest activity during midluteal phase of ovarian cycle
 Declines steadily as plasma levels of progesterone with
regression of the C. Luteum
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PHASES OF MENSTRUAL CYCLE
Figure 5. Phases of the menstrual cycle
OVARIAN CYCLE ENDOMETRIAL CYCLE
A. Follicular Phase A. Proliferative Phase
B. Ovulation Phase B. Secretory Phase
C. Luteal Phase C. Menstrual Phase
D. Pre-Menstrual Phase
OVARIAN CYCLE
FOLLICULAR PHASE
Accdg. to Doc Ilarde (2016 lecture):
 Pre-ovulatory phase (prior to ovulation)
 Estradiol is the predominant hormone
 3 phases of folliculogenesis:
o Recruitment of cohort of antral follicles
- Primordial follicle -> primary pre-antral follicle
- “palaking palaki, FSH has no control”
- Growth factors such as GDF 9 & BMP 15 which
regulate granulosa cell proliferation and
differentiation
- ~ only3 – 7secondary pre-antral follicles will
be selected -> one dominant follicle
- The decrease in estrogen and progesterone of the
previous menstrual cycle suppresses the HPO
axis -> increasing FSH
- FSH – critical signal for cyclic recruitment, “signal
para hindi mamatay lahat ng oocytes”
o Selection of dominant follicle (Graafian follicle)
- Usually only one will complete for growth and
maturity, except twins
- Completed by Day 5 of Follicular Phase
- Dominant follicle is competitive (w/ well-
vascularizedthecal layer (outer) -> more access
to gonadotropins
- Increase estradiol -> increase gonadotropin
receptors -> estrogen production
- However, increase peripheral estradiol will
stimulate negative feedback, signaling the brain
to stop FSH secretion, “para hindi na lumaki ‘yung
ibang follicles, siyalang… siya ‘yung fittest”.
o Growth of the selected dominant follicle
- GnRH frequency is as at its maximum with 1
pulse per 90 minutes -> increasing ovarian
estrogen
- Mean diameter: ~ 18 – 25 mm
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PRE-MENSTRUAL PHASE
 A decline of PROGESTERONE levels will signal the start of
menstruation

Figure 6. Histologic architecture of Graafian follicle

o Granulosa
- avascular
- FSH receptors -> aromatase (androstenedione ->
estrogen)
- Produces inhibin B at early follicular phase ->
inhibiting FSH production after its peak
o Theca Cell
– Theca interna (LH receptors -> androgens)
– Theca externa
o Antrum (fluid filled cavity)

OVULATION PHASE
Accdg. to Doc Ilarde (2016 lecture):
 Middle of ovarian cycle
 Increase estrogen -> reaches threshold -> stimulate HPO
axis -> further increase of FSH and LH production -
>PEAK! (absolute requirement for final oocyte maturation)
 LH PEAK : ~ 10 -12 hours before ovulation
 Resumes meiosis
 Acute inflammatory-like reaction (induced by increased
interleukins, cyclooxygenases)
 Increase progesterone, prostaglandins, GDF 9 & BMP 15 ->
hyaluronan-rich extracellular matrix by cumulus complex
(surrounds the oocyte) -> EXPANSION!
 Proteolytic cascade -> degradation of follicular basement
membrane -> ovulation
 Paradox : LH surge – gives both proteolytic enzymes and
inhibitors (tight regulation of follicular rupture and
formation of corpus luteum)

LUTEAL PHASE
Accdg. to Doc Ilarde (2016 lecture):
 LUTEINIZATION – development of Graafian follicle from
corpus luteum
 After ovulation, granulosa cells will be luteinized ->
vascularized!
 Luteinizing Hormone (LH) – primary luteotropic factor
for corpus luteum maintenance
 Corpus luteum is maintained by low-frequency, high-
amplitude LH pulses
 Hallmark of this phase :PROGESTERONE secretion
 Increase access to more steroidogenic precursors (LDL ->
progesterone)
 14 days is the life span of corpus luteum
 hCG produced by synctitiotrophoblast following
conception rescues the corpus luteum, and maintains
progesterone production
 With no pregnancy: corpus luteum regresses 9-11 days
after ovulation via apoptotic cell death

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ENDOMETRIAL CYCLE FUNCTIONAL LAYER

A. Stratum compactum
A. Proliferative  Site of blastocyst implantantion
B. Secretory  Provides metabolic environment
C. Menstrual B. Stratum spongiosum
 Maintains integrity of the functional layer

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Table 2. The Endometrial Cycle. (based on Dr. Ilarde’s lecture, 2B 2018 trans, and William’s Obstetrics. 24 thed)
ENDOMETRIAL CYCLE
PROLIFERATIVE SECRETORY MESTRUAL
 Proliferation of  Highly predictable: 12-14 days  ~28 days cycle
glandular, stromal and  Continuous development of spiral arteries  3-5 days (2-7 days if regular)
vascular endothelial  Early stage: Endometrial dating is based on glandular epithelium  Average blood loss: ~30 mL (10-
cells histology; after ovulation, the estrogen primed endometrium 80 mL)
responds to rising progesterone levels in a highly predictable  Initiated when production of
 Early stage: ~ 2 mm manner (Wiilliam’s) progesterone in C. luteum drops
thick ; Glands are  2B 2018: Spiral Artery – Essential for establishing the changes as a result of luteolysis
narrow, tubular, in blood flow tht permit either menstruation or implantation  Arterial rather than venous blood
almost straight and loss (rupture of spiral arterioles
parallel course from - glycogen accumulates inthe basal portion of and consequent hematoma
the basalis layer glandular epithelium, creating subnuclear formation)
toward the Day 17 vacuoles and pseudostratification  matrix degradation by
endometrial cavity. - first sign of ovulationthat is histologically proteolytic enzymes (members
Mitotic figures, evident. of MMPs – matrix
especially in the - vacuoles move to the apical portion of the metalloprotease)
glandular epithelium, Day 18
secretory nonciliated cells  Leukocyte infiltration initiates
are identified by the - cellsbegin to secrete glycoprotein and the breakdown and also repair
fifth cycle day mucopolysaccharide contents into the lumen of the functionalis layer
(William’s) - Glandular cell mitosis ceaseswith secretory  Vasoconstriction – there is an
activity due to rising progesterone increase of proinflammatory
 Late stage: Loose levels,which antagonize the mitotic effects of response and regulation of blood
stroma, Glandular Day 19
estrogen. loss.
hyperplasia and - Estradiolaction is also decreased because of
increase stromal glandular expression of thetype 2 isoform of William’s and 2B 2018 trans:
ground substance; and 17-hydroxysteroid dehydrogenase. This  histological characteristic of late
the glands in the convertsestradiol to the less active estrone premenstrual phase: stromal
functionalis layer are - window of implantation infiltration by neutrophils, giving
widely separated. - Epithelial surface cells show decreased a pseudoinflammatory
microvilli and cilia but appearance of appearance to the tissue.
 Midcycle: Glandular luminal protrusions on the apical cell surface  neutrophils infiltrate primarily
epithelium is taller Day 20 –
- These pinopodes are important in preparation on the day or two immediately
and pseudostratified 24
for blastocyst implantation preceding menses onset
with microvilli (which - coincide with changes in the surface  endometrial stromal and
increase epithelial glycocalyx that allow acceptance of a epithelial cells produce
surface area) and cilia blastocyst o interleukin-8 (IL-8) a
( aid in movement of Day 21 – chemotactic–activating
endometrial - stroma becomes edematous
24 factor for neutrophils
secretions during the - stromal cells begin to enlarge, and stromal o monocyte chemotactic
secretory phase) mitosis becomes apparent ; striking changes protein-1 (MCP-1) is
Day 22 - associated with predecidual transformation of synthesized by
 Endometrial dating is 25 the upper 2/3 of the functionalis layer endometrium and promotes
difficult - glands exhibit extensive coiling, and monocyte recruitment
luminal secretions become visible  “inflammatory tightrope” refers
Day 25 – - endothelin and and thromboxin begin to the ability of macrophages to
26 vasoconstriction of spiral arterioles (2B 2018) assume phenotypes that vary
Day 23 – - characterized by predecidual cells, which from proinflammatory and
28 surround spiral arterioles phagocytic to
- Intense vasoconstriction, spiral arteries immunosuppressive and
Day 28
rupture reparative
o relevant to menstruation, in
 The secretory phase is also highlighted by the continuing growth which tissue breakdown and
and development of the spiral arteries. Midluteal secretory phase restoration occur
of the endometrial cycle is a critical branch point in endometrial simultaneously.
development and differentiation

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ANATOMICAL EVENTS DURING MENSTRUATION  Prostaglandins are important in vasoconstriction,

myometrial contractions and upregulation of pro-
 spiral artery coiling becomes sufficiently severe that inflammatory responses, all leading to menstruation
resistance to blood flow increases strikingly, causing
endometrial hypoxia ENDOMETRIUM
o primary cause of endometrial ischemia and tissue ENDOMETRIAL DATING
degeneration
 Vasoconstriction precedes menstruation and is the most
Proliferative Phase
striking and constant event observed in the cycle
 Dating is difficult in this phase because this phase varies in
 Intense spiral artery vasoconstriction also serves to limit
menstrual blood loss. length among women
o Follicular phase (counterpart of proliferative phase
in the ovarian cycle) – ranges from 5-7 days long to
21-30 days
o Whereas, the luteal phase’s (counterpart of
secretory phase in the ovarian cycle) length is
constant at 12-14 days
 Straight to slightly coiled, tubular glands lined by
pseudostratified columnar epithelium with scattered
mitoses

Early Secretory Phase

 Coiled glands with slightly widened diameter lined by simple
columnar epithelium containing clear subnuclear vacuoles
(remember, this is Day 17 in the secretory phase) and
luminal secretions
o Subnuclear vacuoles are the seemingly white spots
below the nucleus of the columnar cells due to
glycogen accumulation

Late Secretory Phase

 Serrated, [more] dilated glands with intraluminal secretion
are lined by short columnar cells
MENSTRUATION
PROSTAGLANDINS Menstrual Phase
Progesterone withdrawal:  Fragmented endometrium with condensed stroma and
 ↑expression of cyclooxygenase 2 (COX-2 or prostaglandin glands with secretory vacuoles are seen in a background of
synthase 2) blood
o synthesize prostaglandins  Apoptosed endometrium is sloughed off and lasts 4 days
 ↓expression of 15-hydroxyprostaglandin dehydrogenase  The functionalis is completely shed as menstrual flow
(PGDH) (arterial and venous blood, remnants of endometrial stroma
o degrade prostaglandins and glands, RBC and WBC)
 ↑prostaglandin production by endometrial stromal cells
 ↑prostaglandin receptor density on blood vessels and CERVICAL GLAND SECRETION
surrounding cells
 The quality and the amount of the cervical mucus are also
During menstruation (progesterone withdrawal): influenced by the production of steroids by the ovaries
 Vasoconstriction (due to ↑prostaglandin) (estrogen and progesterone levels).
 Painful menstruation – likely caused by myometrial  At midcycle (increased estradiol):
contractions nad uterine ischemia o Increasing mucus production by the cervix
o Mediated by prostaglandin-induced spiral artery o Presence of crypts in the cervix
vasoconstriction which causes the uppermost  Needed for the transport and storage of
endometrial zones to become hypoxic spermatozoa
o Hypoxia – inducer of angiogenesis and vascular o Clinically, the mucus is clear and water-like
permeability factors  Under the microscope, it has a fern
appearance when dried

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 Stringy (stretch ~6 cm without breaking) –
“Spinnbarkeit”
 At the luteal phase (major steroid is progesterone):
o Mucus is thickened therefore, less conducive to
sperm transport
o Contraceptive effect: so that sperms can’t pass
through towards the endometrium
SUMMARY OF THE AXIS
*hCG = test for pregnancy. Should be >1500 to be positive.
DECIDUA
 Specialized highly modified endometrium of pregnancy
 Needed for hemochorial placentation – maternal blood
bathes the placenta for nutrient exchange
o One in which maternal blood contacts trophoblast
(Williams, 24th)
FORMATION OF THE DECIDUA
Decidualization
 Transformation of secretory endometrium to decidua
 Depend on level of estrogen and progesterone, and factors
secreted by the implanting blastocyst
(2B 2017 Trans- wala sa PowerPoint ni Doc Ilarde)
 Endometrial development at midluteal phase
o Decidual formation
o Menstruation
 After fertilization, there is continuous production of
progesterone (mainly) and estrogen
 Predecidual changes first appear in the spiral arteries and
arterioles
 Endometrial stromal cells enlarge to form the polygonal or
round decidual cells
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(Williams, 24th – Wala sa PowerPoint ni Doc Ilarde but nasa 2B
2017 trans)
 In human pregnancy, decidual reaction is completed only
with blastocyst implantation.
1. Predecidual changes, commence first during the
midluteal phase in endometrial stromal cells adjacent to
the spiral arteries and arterioles. They then spread
throughout the endometrium.
2. Endometrial stromal cells enlarge to form polygonal or
round decidual cells.
3. The nuclei become round and vesicular and the
cytoplasm becomes clear, slightly basophilic and
surrounded by a transluscent membrane.
4. Each mature decidual cell becomes surrounded by a
pericellular membrane.
 The pericellular matrix may allow attachment of
cytotrophoblasts through cellular adhesion
molecules. The cell membrane may also provide
cell protection against selected cytotrophoblastic
proteases.
PARTS OF THE DECIDUA BASED ON LOCATION
1. Decidua basalis
 portion of the decidua directly beneath the site of blastocyst
implantation that has been modified by trophoblast invasion
2. Decidua capsularis
 the portion overlying the enlarging blastocyst and/or
endothelial cells
 initially separating it from the rest of the uterine cavity
 most prominent during the 2nd month of pregnancy
 Internally contacts the avascular, extraembryonicfetal
membrane, the chorion laeve
3. Decidua parietalis
 lines the remainder of the uterus; found at the peripheral
portion
 growth of conception will obliterate the cavity, there will be
fusion of decidua capsularis and decidua parietalis forming
decidua vera
Figure 6. Parts of the decidua based on location (decidua basalis,
decidua capsularis, and decidua parietalis)
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Decidua parietalis and decidua basalis are composed of 3 layers
(decidua capsularis has only 1 layer):
a. Zona basalis
 with remnants of glands and numerous small blood
vessels and a basal zone
 remains after delivery and gives rise to new
endometrium
b. Zona spongiosa
 a middle portion or spongy zone
c. Zona compacta
 a surface or compact zone
Zona functionalis
 Zona spongiosa + zona compacta
 form the functional zone (hence the name zona
functionalis)
 sloughed off during delivery
DECIDUAL REACTION
 In human pregnancy, the decidual reaction is completed only
with blastocyst implantation.
 Predecidual changes, however, commence first during the
midluteal phase in endometrial stromal cells adjacent to the
spiral arteries and arterioles.
 Thereafter, they spread in waves throughout the uterine
endometrium and then from the site of implantation.
 The endometrial stromal cells enlarge to form polygonal or
round decidual cells.
 The nuclei become round and vesicular, and the cytoplasm
becomes clear, slightly basophilic, and surrounded by a
translucent membrane.
 Each mature decidual cell becomes surrounded by a
pericellular membrane. Thus, the human decidual cells
clearly build walls around themselves and possibly around
the fetus.
 The pericellular matrix surrounding the decidual cells may
allow attachment of cytotrophoblasts.
DECIDUAL BLOOD SUPPLY
Decidua Lost
capsularis
Decidua Persist (spiral arteries)
parietalis
Decidua Unresponsive
basalis
 blood supply of decidua capsularis is lost as the
embryo/fetus grows and expands into the uterine cavity
 blood supply of decidua parietalis persists by spiral arteries
which retain a smooth muscle wall (remain responsive to
vasoagents)
 spiral arteries in decidua basalis are unresponsive
 spiral arterioles and arteries are invaded by the
cytotrophoblasts and during this process, the walls of the
vessels in the basalis are destroyed, leaving only a shell
without smooth muscle
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DECIDUAL HISTOLOGY
 The decidua contains numerous cell types, whose
composition varies with the stage of gestation.
 The primary cellular components are the true decidual
cells, which differentiated from the endometrial stromal cells
and numerous maternal bone marrow-derived cells.
 The zonacompacta consists of large, closely packed,
epithelioid, polygonal, light-staining cells with round nuclei.
Many stromal cells appear stellate, with long protoplasmic
processes that anastomose with those of adjacent cells. This
is particularly so when the decidua is edematous.
 A striking abundance of large, granular lymphocytes termed
natural killer cells (NK) are present in the decidua early in
pregnancy.
 In peripheral blood, there are two subsets of NK cells. About
90% are highly cytolytic and 10% show less cytolytic ability
but increased secretion of cytokines.
 In contrast to peripheral blood, 95% of NK cells in decidua
secrete cytokines. About half of these unique cells also
express angiogenic factors. These decidua NK cells likely
play an important role in trophoblast invasion and
vasculogenesis.
 Early in pregnancy, zona spongiosa of the decidua consists of
large distended glands, often exhibiting marked hyperplasia
and separated by minimal stroma. At first, the glands are
lined by typical cylindrical uterine epithelium with abundant
secretory activity that contributes to nourishment of the
blastocyst.
 As pregnancy progresses, the epithelium gradually becomes
cuboidal or even flattened, later degenerating and sloughing
to a greater extent into the gland lumens. Later in pregnancy,
the glandular elements largely disappear.
 In comparing the decidua parietalis at 16 weeks with the
early proliferative endometrium of a non-pregnant woman,
it is clear that there is marked hypertrophy but only slight
hyperplasia of the endometrial stroma during decidual
transformation.
Nitabuch layer
 zone of fibrinoid degeneration
 invading trophoblasts meet the decidua basalis
 usually absent if the decidua is defective (as in placenta
accreta)
Rohr stria
 more superficial but inconsistent deposition of fibrin
 present at the bottom of the intervillous space and
surrounding the anchoring villi
DECIDUAL PROLACTIN
 The decidua is the source of prolactin that is present in
enormous amounts in amniotic fluid.
 product of the same gene that encodes for anterior pituitary
prolactin
 not to be confused with placental lactogen (hPL), which is
produced only by syncytiotrophoblast
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 Although the amino acid sequence of prolactin in both
tissues is identical, an alternative promoter is used within
the prolactin gene to initiate transcription in the decidua
IMPLANTATION AND
EARLY TROPHOBLAST FORMATION
 Fetus is dependent on the placenta for pulmonary, hepatic,
and renal functions.
 Maternal blood spurts from uteroplacental vessels into the
placental intervillous space and bathes the outer
syncytiotrophoblast, allowing the exchange of gases,
nutrients, and other substances with fetal capillary blood
within the villous core. Thus, fetal and maternal blood are
not normally mixed in this hemochorial placenta.
 A paracrine system which links mother and fetus through
the anatomical and biochemical juxtaposition of the
maternal decidua parietalis and the extraembryonic chorion
leave, which is fetal, is also present.
FERTILIZATION AND IMPLANTATION
 During ovulation, the secondary oocyte and adhered cells of
the cumulus-oocyte complex are freed from the ovary.
 Technically, this mass of cells is released into the peritoneal
cavity, but the oocyte is quickly engulfed by the fallopian
tube infundibulum.
 Further transport is accomplished by directional movement
of cilia and tubal peristalsis.
 Fertilization normally occurs in the oviduct.
 Fertilization must take place within a few hours and no more
than a day after ovulation.
 Due to this narrow opportunity window, spermatozoa must
be present in the fallopian tube at the time of oocyte arrival
(intercourse should occur during the 2 days preceding or
on the day of ovulation).
Zygote
 oocyte + spermatozoa
 diploid cell with 46 chromosomes
 undergoes cleavage after fertilization, producing
blastomeres
 In the two-cell zygote, blastomeres and polar body continue
to be surrounded by the zona pellucida.
 undergoes slow cleavage for 3 days while still in the
fallopian tube
Morula
 product of the cleavage of blastomeres
 12-16 cell stage
 entersuterine cavity3 days after fertilization
Blastocyst (blastula)
 50-60 blastomeres
 gradual accumulation of fluid between morula cells
 58-cell blastocyst
o at 4 to 5 days post-fertilization it differentiates into:
inner cell mass(5 embryo-producing cells) and
trophoblast(53 cells)
o outer cells are called the trophectoderm
 107-cell blastocyst
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Decidua
o not larger than earlier cleavage stages despite the
accumulation of fluid
o 8 formative or embryo-producing cells and 99
trophoblastic cells
o released from zona pellucida secondary to secretion of
proteases from the secretory-phase endometrial glands
 hCG, leukemia inhibitory factor (LIF), colony-stimulating
factor-1 (CSF-1), IL-1𝜶 and IL-1𝜷are blastocyst-produced
cytokines which directly influence the endometrium
(increased trophoblast protease production  degradation of
selected endometrial ECM proteins trophoblast invasion)
Figure 7. Zygote cleavage and blastocyst formation. The morula
period begins at the 12- to 16-cell stage and ends when the
blastocyst forms, which occurs when there are 50 to 60 blastomeres
present. The polar bodies, ashown in the 2-cell stage, are small
nonfunctional cells that soon degenerate.
BLASTOCYST IMPLANTATION
 embryo implants the uterine wall 6 or 7 days after
fertilization
 divided into 3 phases:
o apposition – initial contact of the blastocyst to the
uterine wall
o adhesion – increased physical contact between the
blastocyst and uterine epithelium
 integrins – one of four families of cellular adhesion
molecules (CAMs); cell-surface receptors that
mediate cell adhesion to ECM proteins
 𝜶V𝜷3 and 𝜶4𝜷1 – receptivity marker for
blastocyst attachment
 fibronectin – recognition-site blockade on
integrins which prevent blastocyst attachment
o invasion – penetration and invasion of
syncytiotrophoblast and cytotrophoblasts into the
endometrium, inner third of myometrium, and uterine
vasculature
Trophoblast
 exhibits the most variable structure, function, and
developmental pattern of all placental components
 invasiveness promotes implantation
 nutritional role for the conceptus
[Type text] [Type text] 1.02 Physiology of Menstruation and[Type text]
Decidua

 endocrine organ function essential to maternal physiological 3. Primary neurohormone controlling the reproductive endocrine
adaptations and maintenance of pregnancy axis
 At 8 days post-fertilization, it differentiates into an outer 4. and 5. Two hormones with similar alpha subunits similar to
syncytiotrophoblast and an inner cytotrophoblast. FSH and LH
o Syncytiotrophoblast – amorphous cytoplasm 6. Where can the LH receptor be found?
without cell borders, multiple nuclei, diverse size 7. Where can the FSH receptor be found?
and shape, continuous syncytial lining (this 8. How many oocytes are present at birth?
configuration aids transport) 9. At what day of the follicular phase is the selection of the
o Cytotrophoblast – germinal cells with well- dominant follicle completed?
demarcated cell border, single nucleus, and ability 10. Process wherein corpus luteum development ensues from the
to undergo DNA synthesis and mitosis dominant follicle
 After implantation, trophoblast further differentiates into 11. Where is the site of blastocyst implantation?
villous and extravillous trophoblast. 12. Day of cycle where subnuclear vacuoles are seen in the
o Villous trophoblast – gives rise to chorionic villi, endometrial taking
which primarily transport oxygen, nutrients, and 13. Merging of decidua capsularis and decidua parietalis is called
other compounds between the fetus and mother the ___?
o Extravillous trophoblast – migrate into the 14. What part of the fallopian tube engulfs or catches the
decidua and myometrium and also penetrate secondary oocyte?
maternal vasculature, thus coming into contact 15. Zona compacta and zona spongiosa comprise the ___?
with various maternal cell types; further classified Bonus #1: How many days post-fertilization does the morula
as: enter the cavity of the uterus?
 Interstitial trophoblasts– invade the decidua Bonus #2: Steroid product of granulosa cells
and eventually penetrate the myometrium to form
placental bed giant cells Answers:
 Endovascular trophoblasts – penetrate the 1. proliferative phase
spiral artery lumens 2. Graafian follicle
3. GnRH
REFERENCES: 4. TSH
Dr. Ilarde’s Lecture (2016) 5. hCG
William’s Obstetrics 24thed. 6. theca interna
2B 2017 and 2018 Transes 7. corpus granulosum
8. 2 million
PRE-LEC QUIZ 9. day 5
10. luteinization
1. What is the interval of regular menstruation? 11. zona compacta
2. What is the hormone produced by the hypothalamus? 12. Day 17
3 – 4. What are the hormones produced by the ant. Pituitary 13. decidua vera
gland? 14. fimbrium
5 – 6. Give 2 steroid hormones produced by the ovaries? 15. zona functionalis
7. What is the hormone produced by corpus luteum? Bonus #1: 3 days
8. What is the specialized endometrium of pregnancy? Bonus #2: estradiol
9. What is the product of synctitiotrophoblast that rescues the c.
luteum in pregnancy?
10. Withdrawal of this hormone leads to menstruation?

Answers:
1.28 days
2. GnRH
3. FSH
4. LH
5. Estradiol
6. Progesterone
7. Progesterone
8. Decidua
9. hCG
10. Progesterone

POST-LEC QUIZ

1. What is the equivalent in the endometrial cycle of the follicular

phase in the ovarian cycle?
2. What is the other name of the dominant follicle?

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