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1.1C IMPLANTATION & PLACENTAL DEVELOPMENT

OBSTETRICS

DECIDUA

Endometrium of PREGNANCY

- Essential for HEMOCHORIAL PLACENTATION

Decidualization - dependent on : Estrogen, progesterone &

other factors secreted by blastocyst

During the course of pregnancy, decidual transformation is

from thick to thin.

DECIDUAL STRUCTURE

3 layers

- Zona Compacta Zona Functionalis

- Zona Spongiosa

- Zona Basalis - Remains after delivery, gives rise to new

endometrium

DECIDUAL BLOOD SUPPLY

As a consequence of implantation, blood supply to the decidua

capsularis is lost as the embryo-fetus grows.

Decidua parietalis - spiral arteries

Decidua basalis & intervillous space - invaded by

cytotrophoblasts

Uteroplacental vessels - not responsive to vasoactive agents

Fetal chorionic vessels - transports blood between the placenta

and the fetus

- Contains smooth muscle; doesn't respond to vasoactive

agents

DECIDUAL REACTION

Completed only by blastocyst implantation

Commences mid-luteal phase

DECIDUAL HISTOLOGY

Zona Spongiosa glands

- Cylindrical -> Cuboidal & flat -> Degenerate & Slough off ->

Disappear

Placental Basal Plate (Decidua Basalis)

1. Spongiosa

- Arteries & dilated veins

- Disappeared glands

2. Cell invasion

- Interstitial trophoblast cells

- Trophoblastic giant cells

Normal Decidual Necrosis: 1st to 2nd trimester

Cell types:

- True decidual cells

- Maternal bone marrow - derived cells

- NK cells

- Trophoblast invasion

- Vasculogenesis

PERIPHERAL NK CELLS DECIDUAL NK CELLS

10% Cytokine secretion

90% Cytolytic

95 % Cytokine secretion

50 % Angiogenic

DECIDUAL PROLACTIN

↑↑ in AMNIOTIC FLUID

Paracrine function between maternal & fetal tissues

Same gene that encodes pituitary PRL

- Alternative Promoter - different regulation

Regulation

- Pituitary regulators do not affect decidual PRL

DECIDUAL PROLACTIN ROLES

Amniotic fluid

- Transmembrane solute & water transport

- Fluid volume maintenance

Regulate immunologic functions in pregnancy

- Stimulate T-cells

Protective function

- Repress expression of detrimental genes to pregnancy

IMPLANTATION & FERTILIZATION

IMPLANTATION

Occurs within 6-7 days post fertilization

Must be on 20-24of the endometrial - ovarian cycle

If it doesn't occur within this period: Failure of implantation

o Placenta Previa or Ectopic pregnancy in the cervical wall

o Apposition is the 1st step of implantation

Progestins

Cyclic AMP

Endothelin 1

IL 1

IL 2

EGF

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1.1C IMPLANTATION & PLACENTAL DEVELOPMENT

Obstetrics

FERTILIZATION

With ovulation, the oocyte is engulfed by the fallopian tube

infundibulum. Transport through the tube is by movement of

cilia and tubal peristalsis.

Fertilization, occurs in oviduct in few hours. Spermatozoa must

be present in the tube at the time of oocyte arrival.

Spermatozoa passes between follicular cells; through the zona

pellucida (glycoprotein layer surrounding oocyte Cell

Membrane) and into the oocyte cytoplasm.

Fusion of two nuclei, intermingling of maternal and paternal

chromosomes creates the zygote.

CHORION & DECIDUA DEVELOPMENT

During Early Pregnancy

1. Villi in the entire periphery (chorionic membrane)

2. Blastocysts expand to form DECIDUA (endometrial cavity)

3. Villous trophoblast & anchoring cytotrophoblast, PLACENTA

4. Chorionic villi (Decidua Basalis) form Chorion Frondosum

“Fetal Development of Placenta”

5. Avascular fetal membrane abuts Decidua Parietalis -> Chorion

laeve

End Of 3rd Month

1. Chorion laeve separated from amnion by EXOCOELOMIC

CAVITY

2. Intimate contact to form AVASCULAR AMNIOCHORION

TROPHOBLAST

The peripheral cells of the Blastocyst, which attach the zygote

(fertilized ovum) to the uterine wall and become the placenta

and the membranes that nourish and protect the developing

organism.

FATE OF TROPHOBLAST

During implantation into the uterine wall at 8th day the trophoblast differentiates itself into two layers: o Syncytiotrophoblast (ST)

outer multinucleated syncytium has an amorphous cytoplasm without cell borders has nuclei that are multiple and diverse in size and

shape has a continuous syncytial lining

o Cytotrophoblast (CT)

inner layer of primitive mononuclear cells

germinal cells for the syncytium

has a well-demarcated cell border

has a single nucleus

has the ability to undergo DNA synthesis and mitosis

1 Syncytiotrophoblast (ST)

2 Cytotrophoblast (CT)

3 Epiblast

4 Hypoblast

5 Blastocyst cavity

6 Maternal blood capillary

7 Amniotic cavity

10th day, - the blastocyst becomes

totally encased within the

endometrium

Embryo enlarges - more maternal

decidua basalis is invaded by syncytiotrophoblast

Trophoblastic Lacunae- a system of intercommunicating

channels that permeates syncytiotrophoblast

Lacunae - become filled with maternal blood

FETAL & MATERNAL BLOOD CIRCULATION IN MATURE PLACENTA

MATERNAL CIRCULATION

Physiologic maternal-placental circulation

- Maternal blood thru the basal plate and driven high up to the

chorionic plate

- Blood flows back down as it baths the microvillous surface

- Maternal blood drains back to the venous orifices

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1.1C IMPLANTATION & PLACENTAL DEVELOPMENT

Obstetrics

FETAL CIRCULATION

Deoxygenated blood flows through 2 umbilical arteries

Umbilical vessels branch repeatedly beneath the amnion and

diving villi

Blood with a higher 02 content passes thru the umbilical vein

Placental Surface / Chorionic vessels

- Umbilical vessels along the fetal surface of the chorionic plate

- Responsive to vasoactive substances

- Arteries always cross over the veins

Truncal arteries

- Perforating branches of the surface arteries

- Each supply one cotyledon

- Decrease amount of smooth muscle but has increase in

caliber

AMNION

Provides almost all tensile strength of the fetal membranes

Preterm rupture of fetal membrane - major cause of preterm

delivery

5 separate amnion layers:

> Inner surface - bathed by amnionic fluid, uninterrupted single

layer of cuboidal epithelium

> Basement membrane

> Acellular compact layer - composed primarily of interstitial

collagens

> Outer side of the compact layer - row of fibroblast-like

mesenchymal cells

> Outermost amnion layer - acellular zona spongiosa -

contiguous with the second fetal membrane, the chorion laeve.

DEVELOPMENT

Amniogenic cells - precursor of amnionic epithelium

Growth of amnion eventually engulfs the embryo & prolapses

into the cavity

End of the 1st trimester - apposition of the mesoblast of the

chorion and mnion

AMNION EPITHELIAL CELLS

May respond to signals derived from the fetus of the mother

Responsive to various endocrine or paracrine modulators

Metabolically active:

> Inhibits metalloprotinase-1 synthesis

> Produce PGE2 and fetal fibronectin

> Site of prostaglandin production

> Synthesis of vasoactive peptides

AMNION MESENCHYMAL CELLS

Synthesis of interstitial collagens that compose the compact

layer of the amnion.

Synthesize cytokines that include IL-6, IL-8 and monocyte

chemoattractant protein-1.

Greater source of PGE2 compared to epithelial cells

AMNION TENSILE STRENGTH

Resides almost exclusively in the compact layer

Regulated in part by fibrillar collagen interacting with

proteoglycans such as decorin.

Decorin - promotes tissue strength.

Compact layer:

> Cross linked interstitial collagens I and III

> Lesser amounts of collagens V and VI

Collagen I is the major interstitial collagen in tissues

characterized by great tensile strength, such as bone and

tendon.

Collegen III is believed to contribute to tissue integrity and

provides both tissue extensibility and tensile strength.

THE UMBILICAL CORD

DEVELOPMENT

By middle of the 3rd month, the exocoelom (primitive yolk sac)

is obliterated due to expanding amnion

The amnion fuses with the chorion laeve (non-placental part of

the chorion), and covers the bulging placental disc and the

lateral surface of the body stalk.

This covered body stalk becomes the Umbilical Cord or funis

STRUCTURE & FUNCTION

Dull white in color, is a part of the fetal membranes

Extends from the fetal surface of the placenta to the fetal

umbilicus

Contains three vessels within

Two Arteries and One Vein

Flow into the umbilical vein passes two routes through the

ductus venosus into the inferior vena cava as well as hepatic

circulation

The flow then leaves through the two umbilical arteries

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1.1C IMPLANTATION & PLACENTAL DEVELOPMENT

Obstetrics

These vessels twist within cord, dextral (Right) or sinistral (left)

> It is theorized that crimping of the cord is prevented by

twisting

PLACENTAL HORMONES

BIOLOGIC FUNCTIONS OF hCG

Rescue and maintenance of the corpus luteum

Stimulation of fetal testosterone secretion

Stimulation of the maternal thyroid gland

Relaxin secretion of the corpus luteum

Promotion of uterine vascular vasodilation

Myometrial smooth muscle relaxation

Regulation of expansion of uterine natural killer cell numbers

→ Glycoprotein with a biological activity same to LH

→ Produced almost exclusively by the placenta, however low

levels are also synthesized in the kidney

METABOLIC ACTIONS

Promotes maternal lipolysis

Inhibits leptin secretion

Maternal adaptation to fetal energy requirements

Increase maternal beta cell proliferation to augment insulin

secretion (with prolactin)

Angiogenic -> function in fetal vasculature

→ Lactogenic

→ Growth-hormone like

→ Immunochemical

→ Concentrated in the syncitiotrophoblast

→ Detected as early as 2-3 weeks after fertilization

→ Secreted in the maternal circulation

→ And has low concentrations in the urine

→ Similar with hGH

→ There are five genes in the growth hormone–placental lacto-

gen gene cluster that are linked and located on chromosome

17. Two of these—hPL2 and hPL3—encode hPL, and the

amount of mRNA in the term placenta is similar for each.

→ Within 5 to 10 days after conception, hPL is demonstrable in

the placenta and can be detected in maternal serum as early

as 3 weeks. Maternal plasma concentrations are linked to pla-

cental mass, and they rise steadily until 34 to 36 weeks’ gesta-

tion. The hPL production rate near term—approximately 1 g/

day—is by far the greatest of any known hormone in humans.

The half-life of hPL in maternal plasma is between 10 and 30

minutes. In late pregnancy, maternal serum concentrations

reach levels of 5 to 15 μg/mL.

→ hPL concentration is proportional to placental mass, because

the levels of mRNA for hPL is relatively constant throughout the

pregnancy

→ Energy source for maternal metabolism and fetal nutrition

OTHER PLACENTAL HORMONES

Protein/peptide hormones, analogous to hypothalamic or pituitary

hormone, differ in terms of feedback inhibition.

1. Chorionic Adrenocorticotropic Hormone (ACTH):

Product of Pro-opiomenanocortin.

Placental CRH → Chorionic ACTH, important in fetal

lung maturation and parturition timing.

Promotes glucocorticoid production.

2. Growth Hormone Variant (hGH-V)

GH, synthesized in the syncytium by 21- 26 week’s

of gestation but not expressed in Pituitary.

Growth Promoting and antilipogenic function similar

to hGH but has reduced diabetogenic and lactogenic

actions. Mediates Pregnancy Insulin Resistance.

3. Hypothalamic Releasing Hormones

Analogous of Hypothalamic releasing or inhibiting

hormones.

4. GnRH

Found in cytotrophoblast but not in

cyncytiotrophoblast

Regulates trophoblast hCG production.

5. CRH Related Peotides:

CRH, Ucoroctin, Ucoroctin II and III

CRH level surges (upto 100pmol/L) in third trimester.

Increases trophoblast ACTH secretion. In maternal

plasma CRH binds to CRH-binding protein and

remains inactive.

Induces smooth muscle relaxation in vascular and

myometrial tissues and immunosuppression.

Glucocorticoids stimulates CRH production.

6. GHRH (Grhelin)

Regulator of hGH secretion produced by placental

tissue.

Peaks at midpregnancy and plays role in regulating

hGH-V

7. Relaxin:

Similar to Insulin and IGF-, expressed in Corpus

luteum, decidua and placenta.

Act on myometrium with progesterone to promote

relaxation and quiescence of early pregnancy.

Also plays role in postpartum. extracellular

degradation

8. Parathyroid Hormone Related Hormone (PTH-rP)

Regulate transfer of calcium and other solutes and

fetal mineral homeostasis in bone, amnionic fluid and

circulation.

9. Leptin :

Plays role in birthweights, fetal development and

growth, inhbitis apotosis and promotes trophoblast

proliferation.

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1.1C IMPLANTATION & PLACENTAL DEVELOPMENT

Obstetrics

10. Neuropeptide Y

Expressed in cytotrophoblast, plays role in CRH

release.

11. Inhibin and Activin.

Inhibin produced by trophoblast inhibit pituitary FSH

release thereby inhibiting ovulation during pregnancy

also regulates placental hCG synthesis via GnRH

Activin is expressed in placenta and amnion.

FETAL ADRENAL GLANDS

• At term, it weigh the same as those of the adult.

• More than 85 percent of the fetal gland is composed of a

unique fetal zone

• Daily steroid production of fetal adrenal glands near term is 100

to 200 mg/day.

• The fetal zone is lost in the first year of life and is not present in

the adult.

• In addition to ACTH, fetal adrenal gland growth is influenced by

factors secreted by the placenta.

FETAL ADRENAL HORMONES

PLACENTAL ESTRIOL

SYNTHESIS

FETAL ADRENAL STEROID

PRECURSOR

• Estradiol- primary placental

estrogen secretory product at

term.

• High levels of fetal hepatic 16-

hydroxylase act on adrenal

derived steroids.

• 16-OHDHEA, were converted

to estriol by placental tissue.

• Most placental estrogens are

released into the maternal

circulation.

• Maternal estriol and estetrol

are produced by fetal steroid

precursors.

• There is a severe deficiency

in the expression of 3HSD in

adrenal fetal zone cells

• But there is a very active

steroid sulfotransferase

activity in the fetal adrenal

glands.

The precursor for fetal

adrenal steroidogenesis is

cholesterol.

Fetal adrenal glands

synthesize cholesterol from

acetate.

Enzymes involved in

cholesterol synthesis are

elevated compared with

adult.

It is still insufficient to

account for the steroids

produced by these glands.

Fetal glands take up

lipoproteins as a source of

cholesterol for

steroidogenesis.

LDL was most effective,

HDL was much less, and

VLDL was devoid of

• The principal secretory

products of the fetal adrenal

glands are pregnenolone

sulfate and DHEA-S.

• Cortisol arises primarily in the

neocortex and transitional

zone of the fetal adrenal

glands

stimulatory activity.

Fetal adrenal glands are

highly dependent on

circulating LDL as a source

of cholesterol for optimum

steroidogenesis

The low level of LDL

cholesterol in fetal plasma

results from the rapid use of

LDL by the fetal adrenal

glands for steroidogenesis