2. Scope
• The ovarian – endometrial cycle
• The decidua
• Implantation
• Placenta formation
• Fetal membrane development
3. The Ovarian Cycle
• Follicular phase
• 2 million oocytes at birth
• 400,000 follicles at the onset of puberty
• Remaining follicles are depleted at a rate of
approximately 1000 follicles per month until age
35
• Only 400 follicles are normally released during
female reproductive life
7. Ovulation
• Estradiol ↑ LH surge
• LH surge 10-12 hr ovulation : causes
the oocyte to be released from the follicle .
• The ruptured follicle then becomes the
corpus luteum , which secrets progest
erone.
8. Luteal phase
• The corpus luteum secrets progesterone for only about
11 days in the absence of hCG.
• Progesterone preparation endometrium for
implantation
–Highly vascularized
–glandular secretions
9. The decidua
• Decidualization : transformation of
secretory endometrium to decidua
• Depend on estrogen, progesterone and factors
secreted by the implanting blastocyst.
10. Decidual Structure
• Decidua : 3 parts
1. Decidua Basalis
2. Decidua Capsularis
3. Decidua Parietalis
Decidua Vera = D. Capsulais + D. Parietalis
11. •Decidual parietalis + decidual basalis
like the secretory endometrium
compose of 3 layers
- zona compacta
functional zone
- zona spongiosa
- zona basalis New endometrium after
delivery
12. Decidual reaction
• The decidual reaction is completed only
with blastocyst implantation.
• Predecidual changes
– midluteal phase
– in endometrial stromal cells adjacent to the
spiral arteries and arterioles.
13. Blood supply of the decidua
• The decidua capsularis is lost as the
embryo-fetus grows
• The decidual parietalis spiral artery
,remain : smooth muscle, endothelium
responsive to vasoactive agent
• The decidual basalis spiral artery
14. Decidual histology
• NK are present in the decidua early in
pregnancy
• Play an important role in trophoblast invasion
and vasculogenesis
15. Nitabuch layer
• Zone of fibriniod degeneration in which
invading trophoblasts meet the decidua
• Prevent excessively deep conceptus
implantation (placenta accreta)
16. Decidual prolactin
• Souce of prolactin
• Gene that encodes for anterior pituitary
• Prolactin levels
– in amniotic fluid are extraordinarily high and
may reach 10,000 ng/mL
– in maternal serum 150-200 ng/mL
– Fetal serum 350 ng/mL
(The protein preferentially enters amnionic fluid,
and little enters maternal blood)
17. Roles of Decidual prolactin
• Not clear
1.Transmembrane solute and water
transport, maintenance of amnionic fluid volum
e
2.Regulation of immunological functions
during pregnancy
– Prolactin receptors in bone marrow-derived immune
cells,
– Prolactin may stimulate T cells in an autocrine or
paracrine manner
1.Regulation of angiogenesis during
implantation
2.Repressing expression of genes
detrimental to pregnancy maintenance : i
18. Regulation of decidual prolactin
• Most agents known to inhibit or stimulate
pituitary prolactin
• Secretionincluding dopamine, dopamine
agonists, and
• do not alter decidual prolactin TRH
19. Implantation & Formation of the
Placenta & Fetal membrane
• Fertilization & Implantation
• Biology of the Trophoblast
• Embryonic development after implantation
• Organization of the placenta
• Chorionic villi
• Placental development
20. • Placenta = Pulmonary,Hepatic,
Renal
• Hemochorial type of placenta
• Fetal-Maternal blood not mixed
21. Ovum Fertilization and zygote
Cleavage
• Ovulation : secondary oocyte
Peritoneal cavity
oviduct
Cilia and tubal peritalsis
Fertilization often takes place in ampulla
22. Fertilization
•Sperm penetrates zona pellucida of
secondary oocyte, trigger meiosis II.
•Cortical granule reaction is a propagated
response at the site of sperm entry, and
is a basis for the block to polyspermy.
•Secondary oocyte Meiosis II
mature oocyte
23.
24. • In fallopian tube
: 3 days
1st day : Fertilization
Zygote : diploid cell
2nd day : 2 cell zygote
blastomere
thick zona pellucida
3rd day : Morular
16 cells
25. • In uterine cavity
4th-5th day
Morular = 16 cells
Accumulate fluid -
between cells
Early blastocyst
( 58 cells = 5+53 )
26. Zygot
e Complete meiosis II
Morula – 16 cells
Blastocyst
• Inner cell mass
• Trophoblast
Blastocyst is released from the zona pellucida
IL -1α,IL -1β , hCG: endometrial receptivity
27. Implantation
1. Apposition : most common occurs on the upper
posterior uterine wall
2. Adhesion : Integrins
3. Invasion : Trophoblast
• Implantation occurs 6th or 7th day after fertilization
• Postovulatory production of estrogen &
progesterone by corpus luteum
• 20th -24th day of ovarian-endometrial cycle
28. Trophoblast differentiation
• The formation of the human
placenta : trophectoderm
• Syncytiotrophoblast :
outer multinuclear
• Cytotrophoblast :
inner mononucear
29. Trophoblast differentiation
• After implantation is completed,
trophoblast differentiates in 2 pathways
– Villous trophoblast : chorionic villi
– Extravillous trophoblast : decidua , myometrium
and maternal vasculature
30. 12 th day after fertilization
Chorionic villi
• Primary villi : cytotrophoblast core
• Secondary villi : mesenchymal core
• Tertiary villi : angiogenesis
Villi which failure of angiogenesis >> Hydatidiform
mole
Anchoring villi
• cytrophoblast cells columns
• anchore to the decidua at basal plate
31.
32. Embryonic Development
after Implantation
• 9 th day : Implantation : Blastocysts
Blastocyst wall : uterine cavity single layer with flattened cells
Blastocyst wall : Inner wall Thicker wall, 2 zones
1. Trophoblasts
2. Inner cell mass : embryo-forming
• 10 th day : Blastocyst totally encase within the endometrium
33. Embryonic Development
after Implantation
• 7½ days after fertilization : inner cell mass
or embryonic disc >> ectoderm -mesode
rm - endoderm
• Enclosing space between embryonic disc
and trophoblast : amniotic cavity
• Cells within amniotic cavity condense to
form the body stalk >> Umbilical cord
34.
35.
36. Placental development
• Modification of the maternal vasculature
by trophoblast, occur in the first half
• Important in preeclampsia and IUGR
• Extravillous trophoblast
• Interstitial trophoblast
• Endovascular trophoblast
• Villous trophobast and and anchoring
cytotrophoblast
37. • Interstitial
trophoblast
s
- penetrate
the decidua a
nd
myometrium
-
preparation o
f vss for
endovascular
trophoblasts
• Endovascul
ar
38. The chorion
• The chorion is composed of cytotrophoblasts
and fetal mesodermal mesenchyme that survives
in a relatively low-oxygen atmosphere.
• Chorion frondosum : the area of villi in
contact with the decidua basalis, fetal compone
nt of the placenta
• the chorion laeve : contact with the decidual
capsularis .A portion of the chorion becomes
the avascular fetal membrane that abuts the de
cidua parietalis
39. Maternal Regulation of Trophoblast Invasion
and Vascular Growth
• Decidual natural killer cells (dNK)
– attract and promote invasion of trophoblast into
the decidua and promote vascular growth
– IL-8 and INF-inducible protein-10, VEGF and
placental growth factor (PlGF)
• The extravillous trophoblast: invasion
of endometrium and spiral arteries
• urokinase-type plasminogen activator:
plasminogen plasmin
40. • Trophoblasts are further secured by fetal
fibronectin
• Trophoblast glue
• presence of fFN in cervical or vaginal fluid
is used as a prognostic indicator for preter
m labor
42. Uteroplacental vasculature
Before 12 weeks post fertlization
Invasion and modification of the spiral a. up to the
border of the deciduas and myometrium
12-16 weeks post fertlization
Invasion of the intramyometrium segments of
spiral a.
Remodeling : Dilated , low resistance
uteroplacental vessels
Significance in the pathogenesis of preeclampsia and IUGR
43. Maternal blood flow
• 1 month after conception, maternal
blood enters the intervillous space in “ fou
ntain-like bursts “ from the spiral arterie
s.
• Blood is propelled outside of the maternal
vessels and sweeps over and directly bath
es the syncytiotrophoblast.
• Villous branching : Chorion frondosum >>
Cotyledon :single a and v.
44. Placental growth and maturation
• 1st trimester
Placental growth more rapid than fetal growth
• GA 17 wk by LMP
placental weight = fetal weight
• At term
placental weight = 1/6 of fetal weight
45. At term
Diameter 185 mm
Volume 497 ml
Thickness 23 mm
Weight 508 g
Cotyledon : 10-38
lobes (fibrous septa;
incomplete partition)
46. Placental maturation
At term
• Thin layer of syncytium
• Villi : thin wall capillary
• Significant reduction of cytotrophoblasts
• Decreased stroma
• Increased number of capillary
47. Hofbauer cell
• Fetal macrophage
• Round, vesicular, eccentric nuclei
• Very granular or vacuolated cytoplasm
• Increase in numbers & maturation state out
throughout pregnancy
• Phagocytic , immunosuppressive phenotype
• Produce a variety of cytokines
• Paracrine regulation of trophoblast functions
48. Changes in placental architecture that can cause
decreased efficiency of placental exchange
• Thickening of basal lamina of trophoblast
or capillaries,
• Obliteration of certain fetal vessels
• Fibrin deposition on the villi surface
51. Fetal circulation
•chorionic plate
- chorionic vessels
- responsive to vasoactive agents
•Truncal artery
- perforating branch through chorionic
plate
- supply one cotyledon
•End diastolic flow within umbilical artery
appears at GA 10 wk.
52. Maternal circulation
Basal plate
Intervillous
space
Venous orifice in
basal plate
Uterine vein
53. Maternal circulation
(1) Leave maternal circulation
(2) Flow into an amorphous space lined by
syncytiotrophoblast, rather than capillary end
othelium
(3) Return through maternal veins without
producing arteriovenous-like shunts
that would prevent maternal blood from
remaining in contact with villi long enough for adequ
ate exchange
54. • Spiral arteries : perpendicular to the uteine wall
• Spiral veins : parallel to the uterine wall
• This arrangement aids closure of veins during a
uterine contraction and prevents entry of maternal blo
od from the intervillous space
Principal factors regulating blood flow in
the intervillous space
•Arterial blood pressure
•Intrauterine pressure
•The pattern of uterine contractions
•Factors that act specifically on arterial walls.
56. Immunological Considerations of
the Fetal–Maternal Interface
• Lack of uterine transplantation immunity
• Survival of the conceptus in the uterus
– Decidual natural killer cells with their inefficient
cytotoxic abilities
– Decidual stromal cells
– Invasive trophoblasts
• Placenta : immunologically inert
• Villous trophoblast : absent MHC
antigen(I,II)
• Invasive cytotrophoblast : MHC Class I
57. • Trophoblast HLA (MHC) Class I Expression
– Short arm of Chromosome 6
• Uterine Natural Killer Cells (uNK)
Permit and limit trophoblast invasion
• HLA-G Expression in Trophoblast
only in extravillous cytotrophoblasts
in the decidua basalis and in the chorion laeve
Embryos used for IVF do not implant
if they do not express this soluble HLA-G isoform
58. Amnion
• the inner most fetal membrane
• provide almost all of the tensile strength
of the fetal membrane
• Collagen + fibrous like mesenchymal cell
• avascular
• Lack nerve, lymphatics, smooth muscle
7th or 8th day of embryonic development :
Small sac cover dorsal surface of the embryo >>
engulf embryo>>adhere to chorion leave
59. Structure of Amnion
• The inner
– single layer of cuboidal epithelium
– embryonic ectoderm
• the outer
– A row of fibroblast-like mesenchymal cells
– Embryonic disc mesoderm
• A few fetal macrophages in the amnion
• Lacks smooth muscle cells, nerves, lymphatics,
and importantly, blood vessels
60.
61. Amnion Epithelial Cells
Produce
• PGE2 >> initiation of labor
• fetal fibronectin
• tissue inhibitor of metalloproteinase-1
• brain natriuretic peptide
• CRH
• vasoactive peptide
Mesenchymal Cell
•Fibroblast layer
•Synthesis of
- interstitial collagens (majority of
tensile strength)
- cytokine : IL-6, IL-8, MCP-1
62. Metabolic Function
• contain amniotic fluid
• solute & water transport (maintain AF
homeostasis)
• produce bioactive compounds
AMNIOTIC FLUID
Increase : until GA 34 weeks
At term : 1000 mL
63. Umbilical cord
• Dorsal surface growths faster than ventral surface
• Yolk sac & Allantois is incorporated to form gut
yolk sac: smaller
pedicle: longer
• Middle of 3rd month : amnion fuse with chorion laeve
• Body stalk -> umbilical cord or funis
64. At term
•Cord : 2 arteries, 1 vein
•Rt umbilical v. dissappears early during
development
•Arteries are smaller than vein
Meckel diverticulum
: umbilical vesicle remnant,
: from umbilicus to intestine
The most common vascular anomaly :
absence of 1 umbilical artery
65. Umbilical cord
• Diameter 0.8 - 2 cm
• Length 30 -100 cm (Average 55 cm)
• Abnormal short cord < 30 cm
• Tortious vss which are longer than cord
create nodulation -> false knot
• Spiral vss in cord, prevent clamping
66. •Wharton jelly
- extracellular metrix
- a specialized connective
tissue
- increases in volume at
parturition to assist closure of pla
cental blood vss
