Implantataion, Placental

Development and Abnormalities

Lecturer:
Trician Jan Taguba- Villarosa, MD
Department of OB-GYN
Implantation and Placental Development

Endometrial Cycle
Ovarian and
• MEIOSIS
- process of cell division in the germ cells
to generate sperm and egg cells
- spermatocytes and primary oocytes
undergo DNA replication
- the homologous chromosomes synapse
in pairs except for XY combination to
separate (diploid to haploid)
One primary oocyte= 4 daughter cells (22 plus 1
X chromosomes) to develop into 1 mature
gamete and 3 polar bodies
Meiosis

• From Langman’s Clinical Embryology

• OOGENESIS
- maturation of PGC in females begin before birth

PGC oogoniamitosis primary oocyte

meiosis
growing follicles primordial follicle

primary follicle secondary follicle

secondary oocyte
Development of Oocytes
• Three Stages of Maturation of Primordial
Follicles
1. Primary or preantral stage
2. Vesicular or antral stage
3. Mature vesicular or Graafian follicle
Implantation and Placental Development

Theca cells
Endometrial Cycle
Granulosa cells
Ovarian and
Two-Cell, Two-Gonadotropin Theory
• The increase in gonadotropins (FSH and LH), due
to elevated estrogen levels by the preovulatory
follicles is a precise predictor of OVULATION
- 34 to 36 hours before the ovum is
released from the dominant follicle
-10-12 hours before ovulation, LH
secretion surge, which stimulates
resumption of MEIOSIS in the ovum
and release the first polar body
• Estrogen levels have a more complex pattern of
secretion
-a second increase after ovulation (peak
production of 0.25 mg/day of 17β estradiol, at
midluteal phase)
• Progesterone- 25 to 50 mg/day (midluteal phase)
• Corpus Luteum- continues to produce progesterone
(during pregnancy, due to embryonic hCG)
-degenerates after 9-11 days after ovulation
• Estrogen- regulates follicular development, uterine
receptivity or blood flow in many cells
ENDOMETRIAL CYCLE
• Uterine/Endometrial Cycle
-superficial 2/3 of endometrium (decidua functionalis)
is the zone the proliferates and shed off with each
cycle if fertilization does not occur
-shedding and regeneration occurs almost 400 times
during the reproductive years
Decidua Functionalis- composed of deep intermediate zone
(stratum spongiosum) and superficial compact zone
(stratum compactum)
 Decidua Basalis-deepest portion of the endometrium
-source of endometrial regeneration after each
menses
-decidua basalis is composed of primordial glands
and dense scant stroma after each menses
-proliferation is due to progressive mitosis of the
decidua functionalis in response to E2
-there is evolution of straight, narrow and short
endometrial glands (low columnar pattern) into
longer, tortuous ones (pseudostratified)
• During the early Proliferative Phase
- endometrial thickness is less than 2 mm
thick
-glands are narrow, tubular almost straight
and parallel from the basalis layer to the
endometrial cavity
- at 5th day of cycle (mitotic activity both in
the epithelium and stroma)
-mitotic activity persists until day 16 to 17 or
2 to 3 days after ovulation
Williams Obstetrics 24th Edition
• Secretory/Postovulatory Endometrial Phase
-28-day cycle, ovulation occurs on day 14
-constant at 12 to 14 days
-within 48-72 hours or day 17 (change in
appearance of the endometrium, with eosinophilic
protein-rich secretory products in the
glandular lumen called acid- Schiff positive staining,
glycogen-containing vacuoles)
-progressive edema occurs on the 7th postovulatory
day, spiral arteries are visible, lengthen
and coil
Williams Obstetrics 24th Edition
• Highlight of the Secretory-Endometrium Phase
-predecidual transformation of the upper
2/3 of the functionalis layer (between
days 22 to 25)
- extensive coiling and luminal secretions
(window of implantation from day 20 to
24)
-decreased cellular microvilli
-surface glycocalyx changes allowing the
implantation of the blastocyst
• Late Secretory Phase
-tissue volume decreases
-severe coiling of the spiral arteries and blood
stasis
-hypoxia; vasodilatation
-menstruation ensues
 -cuffing is visible at the perivascular stroma at
day 24, then PMN infiltration and collapse,
breakdown of the decidua functionalis (ischemia)
with the onset of menses
• Menstruation
-results from a withdrawal of endometrial
progesterone (increase in COX 2)
-stromal infiltration with neutrophils,
inflammation, production of IL-8, PGF2α
to cause myometrial contraction and
ischemia, then endometrial surface
sloughs off, hence menstrual bleeding
• Menstrual Bleeding
- spiral arterioles rupture
-hematoma formation
- expansion of the superficial endometrium
followed by rupture
-blood and tissue fragments are sloughed off
- flanges/collars are formed, to restore the
endometrial surface
Fertilization, Implantation
• Acrosomal Reaction- occurs after spermatozoa binds to the zona
pellucida

• Phases of Fertilization
1. Penetration of the corona radiata
2. Penetration of the zona pellucida
3. Fusion of oocyte and sperm cell membranes
Fertilization ( Acrosomal Reaction
and Sperm Penetration)
DECIDUA
• Highly modified endometrium of pregnancy
• Essential for hemochorial placentation (maternal blood contact with
the trophoblast)
• Decidualization- transformation of the secretory endometrium into
decidua (dependent of the estrogen, progesterone and
other factors secreted by the implanting blastocyst)
-endometrial stroma enlarge forming polygonal or
round cells surrounded by pericellular
membrane/matrix to allow cytotrophoblast
attachment
• Three Parts of the
Decidua
1. Decidua Basalis-
modified by
trophoblast
invasion
-directly beneath
the blastocyst
2. Decidua Capsularis-
overlies the
enlarging
blastocyst
-protect the
conceptus from the
rest of the uterine
cavity
3. Decidua Parietalis
• Three Parts of the
Decidua

• The decidua
parietalis and
capsularis become
the decidua vera at
late pregnancy
• Decidua measures 5-
10 mm at early
pregnancy
Placentation

• Three Layers of the Decidua Parietalis

and Basalis
1. Zona Compacta- compact
surface zone
2. Zona Spongiosa- middle spongy
portion
-remnants of glands and
small blood vessels
3. Zona Basalis

Figure 28.7f
• Zona Functionalis- formed by the zona compcta and spongiosa
• Zona Basalis- remains after delivery and regenerates to give rise
to a new endometrium
• Decidual Reaction in
Pregnancy
-completed by blastocyst
implantation
-endometrial stroma
enlarge forming polygonal
or round cells surrounded
by pericellular membrane/
matrix to allow
cytotrophoblast attachment
• Blood supply to the decidua capsularis is lost as the fetus-embryo
continues to grow
• Blood supply to the decidua parietalis persists
• Nitabuch Layer
- zone of fibrinoid layer where the decidua basalis
meets the invading trophoblast
• Rohr Stria- more superficial but inconsistent deposition of fibrin
• Decidual Prolactin
-similar to anterior pituitary prolactin
-exact physiological role is unknown
-enters into the amniotic fluid to serve in
transmembrane solute and water transport in amniotic
fluid volume maintenance
-may stimulate T cells regulating immunological
function during pregnancy
-plays a role in the angiogenesis regulation during
implantation
Implantation and Placental Development

Theca cells
Endometrial Cycle
Granulosa cells
Ovarian and
• The increase in gonadotropins (FSH and LH), due to elevated estrogen
levels by the preovulatory follicles is a precise predictor of
OVULATION
- 34 to 36 hours before the ovum is released from the
dominant follicle
-10-12 hours before ovulation, LH secretion surge,
which stimulates resumption of MEIOSIS in the ovum
and release the first polar body
Fertilization, Implantation
• Acrosomal Reaction- occurs after spermatozoa binds to the zona
pellucida

• Phases of Fertilization
1. Penetration of the corona radiata
2. Penetration of the zona pellucida
3. Fusion of oocyte and sperm cell membranes
Fertilization ( Acrosomal Reaction
and Sperm Penetration)
Events After Fertilization
Zygote Cleavage and
Blastocyst Formation
Cleavage: From Zygote to Blastocyst
Degenerating Inner cell mass
zona pellucida
Blastocyst cavity
Blastocyst
cavity Trophoblast
(a) Zygote (b) 4-cell stage (c) Morula (d) Early blastocyst (e) Implanting
(fertilized egg) 2 days 3 days 4 days blastocyst
6 days

Fertilization (a)
(b)
(sperm meets (c)
egg)

Uterine tube Ovary

Oocyte (d)
(egg)

(e)
Ovulation Uterus

Endometrium
Cavity of
uterus

Figure 28.4
Implantation of the Blastocyst
• On the 6th or 7th day after fertilization
-implantation of the embryo into the uterine wall
Three Phases of Invasion
1. apposition- initial contact of the blastocyst to the uterine wall
(upper uterine wall)
2. adhesion- increased contact between the blastocyst and the
uterine epithelium
3. invasion- penetration and invasion of the syncytiotrophoblast
and cytotrophoblast into the endometrium, inner
third of the myometrium and uterine vasculature
Implantation of the Blastocyst

Figure 28.5a
Partially Implanted Blastocyst

Figure 28.5b
• Day 8 of Development
- the blastocyst is partially embedded in the
endometrial stroma
Trophoblast differentiates into two layers:
a. Cytotrophoblast (inner layer of mononucleated cells)
b. Syncytiotrophoblast (outer multinucleated zone
without distinct cell boundaries)
• Uterine Receptivity- occurs during days 20 to 24 of the cycle
-receptive endometrium is primed by estrogen and
progesterone by the corpus luteum
• Hypoblast layer- layer of small cuboidal cells
adjacent to the blastocyst cavity

• Epiblast layer- layer of high columnar cells

adjacent to the amniotic cavity
- give rise to the amniotic cavity

• Amnioblast- epiblast cells adjacent to the

cytotrophoblast
Blastocyst to Embryonic Development

Figure 28.7a-c
• Day 9 of Development
- deep implantation of the blastocyst into the
endometrium
- formation of trophoblastic lacunae (lacunar
stage)
- exocoelomic membrane give rise to the
exocoelomic cavity of primitive yolk sac
• Days 11 and 12 of Development
- complete implantation of the blastocyst
- further development of trophoblastic
lacunae forming an intercommunicating
network
- syncytiotrophoblast cause erosion of the
endothelial lining of the maternal capillaries to
establish uteroplacental circulation
• Sinusoids are formed due to the swelling of the
maternal capillaries
• Day 13 of Development
- implantation bleeding (near 28th day of
mentrual cycle) may occur as a result of
increased blood flow towards the lacunar
spaces
- formation of the primary villi and chorionic
cavity (extraembryonic coelom)
-development of the definitive/secondary
yolk sac
-connecting stalk is visible which becomes the
umbilical cord
LACUNAR FORMATION WITHIN THE
SYNCYTIOTOPHOBLAST
 PLACENTAL ORGANIZATION

• CHORIONIC VILLI
-deeper blastocyst
invasion give rise to a
solid primary villi (from
the extravillous
cytotrophoblast)
-arise from the
cytotrophoblast
protruding into the
syncytium before the
12 th day of fertilization
• During the 17th day
-fetal blood vessels are functional and
placental circulation is established
-completion of the fetal –placental
circulation occurs when the embryonic
blood vessels connect with the
chorionic vessels
• Langhan’s cells- layer of cytotrophobalst surrounded by the
syncytium
• One pole of the developing embryo faces the endometrial cavity
while the opposite pole form the placenta from villous
trophoblast and anchoring cytotrophoblast
• Chorionic villi in
contact with the
decidua basalis
becomes the chorion
frondosum (leafy
chorion- fetal
component of the
placenta)
• Development of the
embryo cause a
cessation of blood
supply to the chorion
facing the endometrial
cavity becoming the
avascular fetal
membrane that abuts
the decidua parietalis
(chorion leave or
smooth chorion)
• At this time of development, maternal circulation
bathes the syncytiotrophoblast
• Each of the truncal or main stem villi and their
ramifications (rami) constitutes a placental lobule, or
cotyledon. Each lobule is supplied with a single truncal
branch of the chorionic artery. And each lobule has a
single vein so that lobules constitute functional units
of placental architecture
• During the first trimester, the placental growth is
more rapid than fetal growth
• Placental and fetal weights become
approximately equal during 17 postmenstrual
weeks
• At term, the placenta will only weigh 1/6th of the
fetal weight
• Cotyledons or lobes (10 to 38) are functional
units supplied by the main stem villi
• Changes in the Placenta
1. fetal vessels become more prominent
2. villous stroma becomes denser and spindle cells
become closely packed
3. stroma is infiltrated by Hofbauer cells (fetal
macrophages)
4. increased transport and nutrient exchange
• Oxygenated
blood is
supplied to the
fetus through
the single
umbilical vein