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Subject Topic Date Lecturer

OB-GYN

Tranx No. 2

The Decidua, Placenta, and Placental Hormones 2009 December 14 Vincent Fortun, MD
Pages

Batch 2012 / 2009-2010

Transcriber Ron Cortez Subject Head

Ronnelaine Cortez

OUTLINE
I. II. III. IV. The Decidua The Placenta Placental Hormones Abnormalities of Fetal Membranes

Sources: Past Tranx, Williams Obstetrics, and Recordings

I. A. The Decidua

THE DECIDUA

Highly specialized and modified endometrium of pregnancy

B. Functions of the Decidua:


1. 2. 3. 4. Facilitates apposition and implantation of the blastocyst Serves as an immunologically specialized tissue Accepts trophoblast invasion, thus providing for embryo-fetal nutrition Contributes cytokines and growth factors that promote placental growth, function, and the inhibition of trophoblast apoptosis

C. Structure of the Decidua: (Must-know terms)


1. Decidua basalis the portion directly beneath the site of blastocyst implantation 2. Decidua capsularis the portion overlying the enlarging blastocyst 3. Decidua parietalis the portion covering the remainder of the uterus

D. Layers of the Decidua:


1. Zona compacta surface of the decidua 2. Zona spongiosa the middle portion of the decidua 3. Zona basalis remains after delivery and gives rise to the new endometrium (Favorite board question) *Zona functionalis = zona compacta + zona spongiosa *May also be referred to as stratum compacta, stratum spongiosa, and so on.

E. Vascular Supply
The spiral arteries of the decidua are a very prominent organ/structure. They arise from the arcuate arteries which are branches of the uterine vessels. These are the high-pressure blood vessels bringing oxygenated blood to the decidua. The ovarian and endometrial cycles specific modifications in the rate of blood flow in these arteries are essential for: 1. The initiation of menstruation 2. The limitation of blood loss in the menses

F. Menstruation
Menstrual bleeding is of both arterial and venous origin. (But arterial bleeding is, quantitatively, appreciably greater than venous.)

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G. Physiology of How Menses Occur:


rhexis or rupture of an arteriole of a spiral artery hematoma formation superficial endometrial distention and rupture fissures develop in the adjacent functional layers blood and tissue are detached or sloughed off appearance of menstrual blood in the vagina

II. THE PLACENTA


Supplies all materials required for fetal growth and energy production while removing products of fetal catabolism. Provides nutrition and takes care of waste products during the pregnancy. Provides much insight into prenatal life Results of its examination are often helpful in caring for the neonate. (So its important for pediatricians as well.) Gives a record which pediatricians and obstetricians can use to plan for the future care of the mother and the child. The placenta has two sides: 1. Fetal side 2. Maternal side

smooth, shiny, and relatively free of blood bloody, dark red, with lobes and cotyledons

HEMOCHORIOENDOTHELIAL PLACENTATION o Unique to humans o At all sites of direct cell-to-cell contact, maternal tissues (both eciduas and blood) are juxtaposed (closely attached) to extraembryonic cells (trophoblasts) and NOT to the embryonic cells or fetal blood. o There is no mixing of fetal and maternal blood. Otherwise, problems will occur. There is always an intervening structure. o Maternal blood in the intervillous space directly bathes the trophoblasts. Transfer of substances (oxygen, nutrients) from mother to fetus is accomplished first by transfer from the intervillous space into the syncytiotrophoblast. Theres no direct transfer from maternal to fetal blood.

A. EARLY HUMAN DEVELOPMENT (Review) (Take note of the chronology. Again, common board exam question.)
Fertilization of the egg by a spermatozoan occurs in the fallopian tube. A common misconception is that fertilization occurs in the uterus. The mature ovum becomes a zygote (a diploid cell with 46 chromosomes). Zygote undergoes cleavage to form blastomeres. Sixteen or so blastomeres form a solid ball called morula (3rd to 4th day after fertilization takes place). The blastocyst is formed after the morula reaches the uterus (usually 6-7 days after fertilization), with the formation of a fluid-filled cavity within it. The inner cell mass gives rise to the embryo. Embryonic period lasts until the end of the 7th week. After embryonic period, the developing conceptus is referred to as the fetus. *Remember: Before 7 weeks AOG = embryonic period After 7 weeks AOG = the conceptus is now called the fetus 1. IMPLANTATION The blastocyst adheres to the endometrium of the uterus. (~7 days after fertilization) The implanting blastocyst becomes completely buried in and covered by the endometrium.
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2. TROPHOBLAST A very specialized cell, Dr. Fortuns favorite cell: Without it, you and I would not be here. Responsible for implantation Its invasiveness provides for attachment of the blastocyst to the uterus. Role in nutrition of the conceptus Endocrine function is essential to maternal physiological adaptations and the maintenance of pregnancy 2 kinds: Cytotrophoblast and Syncytiotrophoblast Becomes the bane of women in trophoblastic cancer. CYTOTROPHOBLAST Well-demarcated borders Single, distinct nucleus Frequent mitosis Cellular progenitors of the syncytiotrophoblasts Produce cellular enzymes which allow it to move between and attach to endometrial epithelial cells during blastocyst implantation. Pale-staining SYNCYTIOTROPHOBLAST No cell borders Nuclei are multiple and diverse in size and shape Amorphous cytoplasm Controls transport processes across the synctia (very important for fetal nutrition) Secretes hormones (most important function) Very dark-staining because of very high nuclear activity

*How come the developing embryo is able to attach itself into the endometrium of the mother when 50% of its DNA is foreign? Normally, when there is something foreign that enters our body, our immune system tends to destroy that foreign body. The wonder of pregnancy is in the immunologic acceptance of the fertilized ovum.

B. IMMUNOLOGIC ACCEPTANCE OF THE CONCEPTUS


Human Leukocyte Antigen-G (HLA-G) is expressed exclusively by cytotrophoblasts, and is monomorphic (self); thus, does not evoke an immunological response by maternal immune cells against fetal trophoblasts. The regulation of HLA-G Class I antigen expression on extravillous cytotrophoblasts may be crucial in first allowing, and then inhibiting cytotrophoblast invasion of the endometrium/decidua and spiral arteries.

C. PLACENTAL DEVELOPMENT
After blastocyst implantation, cytotrophoblasts proliferate rapidly and invade the surrounding decidua. Anchoring and villous trophoblasts form the early placenta. Walls of superficial decidual capillaries are eroded and the walls of spiral arteries are destroyed. (The fertilized ovum is a parasite, so it has to find source of nutrition and oxygen for it to survive. Hence, the trophoblasts now seek out these capillaries/arteries.) Maternal blood directly bathes the syncytiotrophoblasts in the intervillous space (14th to 15th day of life).

MUST-KNOW! Villi in contact with the decidua basalis proliferate to form the chorion frondosum (the fetal component of the placenta). Villi in contact with the decidua capsularis degenerate to form the chorion laeve. After the 3rd month, the chorion laeve and the amnion come into contact and form the amniochorion/fetal membranes.

D. PLACENTAL BARRIER
Substances that pass from maternal to fetal blood must first traverse: 1. Syncytiotrophoblast 3 components of the placental barrier 2. Stroma of the intravillous space 3. Fetal capillary wall However, the placenta does not maintain absolute integrity of the fetal and maternal circulations at times such as in cases of erythroblastosis fetalis.

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E. PLACENTA AT TERM
185 mm in diameter 23 mm in thickness 497 ml average volume 508 g weight 10 to 38 cotyledons (cotyledons separated by septae)

F. PLACENTAL AGING
Decreased thickness of syncytium Formation of syncytial knots (stroma within the placenta) Villous stroma, Hobauer cells, and Langhans cells are reduced Thickening of the basement membranes of the capillaries and trophoblasts (very important because if theres thickening of the basement membrane, there is less amount of oxygen and nutrients that can reach placental circulation) Obliteration of certain fetal vessels Deposition of fibrin on the surface of villi, basal and chorionic plates, and intervillous space
*The placenta degrades as the pregnancy nears term, this is why we dont want post-term babies (>42 weeks AOG)

G. FETAL CIRCULATION (Must memorize)


Fetal deoxygenated blood flows to the placenta through the two umbilical arteries. At the juncture of the umbilical cord with the placenta, the umbilical vessels branch repeatedly (chorionic arteries to truncal arteries) to form capillary networks in the terminal divisions of the villi. Blood with a higher oxygen content returns from the placenta to the fetus through a single umbilical vein. Common Evals/Board Exam Questions: Which blood vessel has a higher oxygen content: the umbilical vein or the umbilical artery? How many umbilical veins are there? How many umbilical arteries?

H. MATERNAL CIRCULATION
Maternal blood enters the intervillous space in spurts produced by maternal blood pressure. Blood is then forced toward the chorionic plate. Lateral spread of blood occurs. Arterial pressure forces blood toward exits in the basal plate to the uterine veins During uterine contractions, both inflow and outflow are curtailed, while the volume of the blood in the intervillous space is maintained; thus, providing for continuous exchange. Even if the uterus is contracting vigorously during labor, there is still an adequate amount of blood within the placenta to maintain constant exchange of nutrients and waste products between maternal and fetal blood.

I.

ABNORMALITIES OF PLACENTATION

(Definitions from Williams Obstetrics, 22nd ed.)

Multiple placentas with a single fetus - The placenta occasionally is separated into lobes. When the division is incomplete and the vessels of fetal origin extend from one lobe to the other before uniting to form the umbilical cord, the condition is termed placenta bipartita or bilobata. If the two or three distinct lobes are separated entirely, and the vessels remain distinct, the condition is designated placenta duplex or placenta triplex. Succenturiate placenta - An extra placenta separate from the main placenta. In anatomy, "succenturiate" means substituting for or accessory to an organ. In this case, a succenturiate placenta is an accessory placenta. Ring-shaped placenta - the placenta is annular in shape, and sometimes a complete ring of placental tissue is present. Because of tissue atrophy in a portion of the ring, a horseshoe shape is more common. Membranous/Membranaceous placenta - Very rarely, all of the fetal membranes are covered by functioning villi, and the placenta develops as a thin membranous structure occupying the entire periphery of the chorion. This finding is called placenta membranacea and also is referred to as placenta diffusa. Fenestrated placenta - In this rare anomaly, the central portion of a discoidal placenta is missing. In some instances, there is an actual hole in the placenta, but more often the defect involves only villous tissue with
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the chorionic plate intact. Clinically, it may be mistakenly considered to indicate that a missing portion of placenta has been retained in the uterus. Extrachorial placenta - A placenta in which there is a rim of placental tissue that extends beyond the vascular plate, accompanied by fibrin on the margin. Large/Mega placenta Placental polyp

J.

PLACENTA: CIRCULATORY DISTURBANCES Infarcts Calcification Villous (fetal artery thrombosis)

K. THE AMNION
Identifiable at the 7th to 8th day of embryonic development The innermost fetal membrane (contiguous with the amniotic fluid) Provides almost all of the tensile strength of the fetal membrane (Evals Question) Does not contain smooth muscles, nerves, lymphatics, and blood vessels. o Used as biological dressings since the tensile strength is good and no other structures are prone to degradation

1. Development of the Amnion At the 7th or 8th day of embryonic development, the amnion develops into a small sac that covers the dorsal surface of the embryo. Amnion enlarges and covers the whole embryo Comes into contact with the interior surface of the chorion laeve Apposition of the chorion laeve and amnion causes obliteration of the extraembryonic coelom 2. Layers of the Amnion Epithelium Basement membranes Compact layers o Responsible for tensile strength Mesenchymal cell layer Zona spongiosa 3. Metabolic Functions of the Amnion Transports solutes and water to maintain amniotic fluid homeostasis Produces vasoactive peptides (no need to memorize) o Endothelin-1 o Parathorome-related protein o Enkephalinase o Brain natriuretic peptide o Cortocotropin-relaxing hormone Secretes growth factors and cytokines 4. Amniotic Fluid Clear Increases in quantity as pregnancy progresses till near term Average volume: 1,000 mL In early pregnancy, it is an ultrafiltrate of maternal plasma. By the 2nd trimester, it consists largely of extracellular fluid which diffuses through the fetal skin. After 20 weeks, it is composed largely of fetal urine. Pulmonary fluid and fluid filtering through the placenta also contribute.

5. Chorioamnionitis Inflammation of the fetal membranes Frequently associated with prolonged membrane rupture and long labors
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Mononuclear and polymorphonuclear leukocytes infiltrate the chorion (a pathologic diagnosis) Managed by antibiotics and immediate delivery (otherwise, the baby will have sepsis)

L. THE UMBILICAL CORD


Extends from the fetal umbilicus to the fetal surface of the placenta (chorionic plate). Dull white, moist, covered by amnion 0.8 to 2.0 cm in diameter 55 cm in length False knots are varices caused by folding and tortuosity of the blood vessels The umbilical vein carries oxygenated blood to the fetus. The right umbilical vein disappears as it develops. The two umbilical arteries carry deoxygenated blood from the fetus to the placenta.

III. PLACENTAL HORMONES


The production of steroid and protein hormones by human trophoblasts is greater in amount and diversity than that of any endocrine tissue known in all mammalian physiology or pathophysiology. A. HUMAN CHORIONIC GONADOTROPIN (hCG) pregnancy hormone A glycoprotein structurally related to and with biological activity very similar to Luteinizing Hormone (LH), Follicle-Stimulating Hormone (FSH), and Thyroid-Stimulating Hormone (TSH) Produced almost exclusively in the placenta specifically by syncytiotrophoblasts Produced by malignant tumors (trophoblastic cancers) Produced in small amounts by the anterior pituitary glands of both men and women. Nobody knows why even men produce hCG. 1. Molecular Forms of hCG Intact hCG molecule o Rate of secretion is maximal at 8 to 10 weeks of pregnancy. After that, its level slowly goes down but even if it goes down, it does not go back to normal. Beta subunit o most important because it is easily measurable by present-day technology. Free alpha, nicked hCG, and beta-core fragment are very difficult to measure. Free alpha subunit Nicked hCG molecule Beta-core fragment of hCG

2. hCG Concentrations in Pregnancy hCG enters maternal blood at the time of blastocyst implantation (about 7-9 days post-ovulation Concentration in the maternal plasma is equal to the concentration in maternal urine o Before the advent of urine testing, we used to determine if a woman is pregnant by getting a blood sample. 1,000 mIU/mL = 6 weeks of pregnancy 100,000 mIU/mL = 8 to 11 weeks of pregnancy Concentrations in the plasma start to decline at 10 weeks (nadir at 20 weeks) In normal single pregnancies, the level should not go beyond 100,000 mIU/mL 3. Conditions with Elevated hCG levels (>100,000 mIU/mL) Pregnancies with multiple fetuses Erythroblastotic fetus Syphilis in pregnancy H-mole or choriocarcinoma Fetus with Down Syndrome Non-trophoblastic tumors (germ cell tumors) 4. Conditions with Depressed hCG levels Ectopic pregnancy
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Impending spontaneous abortion Death of fetus 5. Biologic Functions of hCG rescue and maintenance of function of the corpus luteum MOST IMPORTANT Stimulation of fetal testicular testosterone secretion o Promote male sexual differentiation Were it not for hCG, all of us would be females Stimulation of maternal thyroid gland Promotes relaxin secretion by corpus luteum

B. HUMAN PLACENTAL LACTOGEN (hPL) Concentrated in syncytiotrophoblasts (5 weeks) Maximal concentrations at 34-36 weeks Rate of secretion is proportional to placental mass o Low levels in trophoblastic disease patients Also secreted by malignancies other than that of trophoblast or of gonad o Bronchogenic Ca, hepatoma, lymphoma, pheochromocytoma Metabolic Functions of hPL Lipolysis and increased levels of free fatty acids o Provides source of energy for maternal metabolism and fetal nutrition Anti-insulin action o Increased maternal insulin levels favors protein synthesis for transport to the fetus. C. ESTROGEN Human pregnancy is an hyperestrogenic state Syncytiotrophoblast secretes two estrogens: o Estradiol-17 Beta o Estriol Promotes growth of the endometrium D. PROGESTERONE Produced by syncytiotrophoblast Facilitates and permits the maintenance of pregnancy Formation occurs through the uptake and use of maternal LDL cholesterol E. OTHER PROTEIN HORMONES OF THE PLACENTA (No need to memorize) Chorionic Adenocorticotropin Chorionic Thyrotropin Hypothalamic-like Releasing Hormones Relaxin o Promotes uterine relaxation Parathyroid Hormone-related Protein o PTH of fetus Human Growth Hormone-Variant o Biological activity similar to hPL Neuropeptide-Y Inhibin o In conjunction with sex steroids, may serve to inhibit FSH secretion during pregnancy (no ovulation) Activin Atrial Natriuretic Peptide o Promotes uterine relaxation

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IV. ABNORMALITIES OF THE FETAL MEMBRANES


Review: The amniotic fluid, in early pregnancy, is an ultrafiltrate of maternal plasma. By the 2nd trimester, it consists largely of extracellular fluid. After 20 weeks, it is composed largely of fetal urine. A. MECONIUM STAINING Meconium o The first material excreted by the fetus via the anus. o Composed of exfoliated gastrointestinal tract cells of the fetus o However, if in the time of birth, when the baby takes his first breath and aspirates the meconium, it can cause irritation of the fetal lungs. Occurrence increases after 40 weeks AOG Passage is associated with increased perinatal morbidity and mortality due to meconium aspiration CHORIOAMNIONITIS Inflammation of the fetal membranes A manifestation of intraamnionic infection Frequently associated with prolonged membrane rupture and prolonged labor Treatment: antibiotics and immediate delivery HYDRAMNIOS Amniotic fluid of >2,000 mL volume Amniotic fluid index of >24 cm (via ultrasound) Presence is associated with fetal malformations, especially of the central nervous system (e.g., anencephaly, spina bifida) or gastrointestinal tract (e.g., esophageal atresia); and in monozygotic twin pregnancies Symptoms result from pressure exerted within and around the overdistended uterus upon the adjacent organs. The more severe the degree of hydramnios, the higher the perinatal mortality rate; causes fetal malformations, chromosomal abnormalities, preterm labor Maternal complications: o Placental abruption o Uterine dysfunction o Postpartum hemorrhage Management: o Amniocentesis o Amniotomy OLIGOHYDRAMNIOS Amniotic fluid index of 5 cm or less Fetal outcome is poor Conditions associated: o Fetal chromosomal abnormalities, post-term pregnancy o Placental abruption, twin-twin transfusion o Maternal hypertension, preeclampsia, diabetes in pregnancy o Drugs prostaglandin synthetase inhibitors o Idiopathic Management: o Amnioinfusion during labor (adding more amniotic fluid into the sac) not done in UMC as it is very complicated o Abdominal delivery It depends. Among obstetricians, if they see an oligohydramnic mother who is less than 5cm dilated, they usually deliver abdominally. But if the mother is 7-9 cm dilated, they still opt for a vaginal delivery with close monitoring. -END OF TRANSCRIPTIONThose with are the ones Dr. Fortun gave importance to in the lecture

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