Placenta & Extraembryonic Membranes PDF

PLACENTA, EXTRAEMBRYONIC MEMBRANES & MULTIPLE PREGNANCIES Gizem SÖYLER, PhD Near East University Faculty of Medicine Department of Histology & Embryology  The placenta and fetal membranes separate the fetus from the endometrium, the inner layer of the uterine wall. An interchange of substanc...

PLACENTA, EXTRAEMBRYONIC MEMBRANES & MULTIPLE PREGNANCIES Gizem SÖYLER, PhD Near East University Faculty of Medicine Department of Histology & Embryology  The placenta and fetal membranes separate the fetus from the endometrium, the inner layer of the uterine wall. An interchange of substances, such as nutrients and oxygen, occurs between the maternal and fetal bloodstreams through the placenta. The vessels in the umbilical cord connect the placental circulation with the fetal circulation. The fetal membranes include the chorion, amnion, umbilical vesicle, and allantois. PLACENTA The placenta is the primary site of nutrient and gas exchange between the mother and embryo/fetus. The placenta is a fetomaternal organ that has two components: A fetal part that develops from the chorionic sac, the outermost fetal membrane A maternal part that is derived from the endometrium, the mucous membrane comprising the inner layer of the uterine wall  The placenta and umbilical cord form a transport system for substances passing between the mother and embryo/fetus. Nutrients and oxygen pass from the maternal blood through the placenta to the embryo/fetal blood, and waste materials and carbon dioxide pass from the fetal blood through the placenta to the maternal blood.  The placenta and fetal membranes perform the following functions and activities: protection, nutrition, respiration, excretion of waste products hormone production. Shortly after birth, the placenta and membranes are expelled from the uterus as the afterbirth. DECIDUA The decidua is the endometrium of the uterus in a pregnant woman. It is the functional layer of the endometrium that separates from the remainder of the uterus after parturition (childbirth). The three regions of the decidua are named according to their relation to the implantation site: The decidua basalis is the part of the decidua deep to the conceptus (embryo/fetus and membranes), which forms the maternal part of the placenta. The decidua capsularis is the superficial part of the decidua overlying the conceptus. The decidua parietalis represents the remaining parts of the decidua.  As progesterone levels rise in maternal blood, connective tissue cells in the decidua (the uterine lining) enlarge and become pale-staining decidual cells, accumulating glycogen and lipid in their cytoplasm. These changes, known as the decidual reaction, occur as the blastocyst implants.  Decidual cells near the chorionic sac, along with maternal blood and uterine secretions, provide essential nutrition for the embryo/fetus. These cells may also protect maternal tissue from uncontrolled invasion by the syncytiotrophoblast (the outer layer of the trophoblast) and could play a role in hormone production. Decidual regions are visible in early pregnancy ultrasounds and are important for diagnosis. Development of Placenta The placenta develops from the trophoblast (the outer layer of the blastocyst) and the extraembryonic mesoderm, forming the chorionic plate. Early in development, the trophoblast rapidly proliferates, leading to the formation of the chorionic sac and chorionic villi. These villi initially cover the entire chorionic sac, but as the sac grows, villi associated with the decidua capsularis (the outer part of the decidua) degenerate, leading to the formation of the smooth chorion (chorion laeve). In contrast, villi associated with the decidua basalis (the part of the decidua beneath the embryo) grow and branch extensively, forming the villous chorion (chorion frondosum), which becomes the fetal part of the placenta.  The placenta has two main parts: 1. Fetal part: Derived from the chorionic villi, which arise from the chorion and project into the intervillous space containing maternal blood. These villi are essential for nutrient and gas exchange between the mother and the fetus. 2. Maternal part: Derived from the decidua basalis of the endometrium, which is eroded by the invading chorionic villi, creating a large intervillous space filled with maternal blood.  As the placenta matures, a complex vascular network forms, facilitating the exchange of gases, nutrients, and waste products between the mother and fetus. The cytotrophoblast cells undergo an epithelial-to- endothelial transition, enabling them to invade maternal spiral arteries, transforming these vessels into low- resistance channels that provide a steady supply of maternal blood to the intervillous spaces. Over time, the chorion laeve (smooth chorion) fuses with the decidua parietalis, obliterating the uterine cavity and further establishing the placenta.  By the fourth month, the placenta is well-established, with the maternal part almost entirely replaced by the fetal villous structures. The syncytiotrophoblast, the outer layer of the trophoblast, becomes thin, allowing for efficient exchange between the maternal and fetal circulations. The fully developed placenta covers 15% to 30% of the decidua and weighs about one-sixth as much as the fetus.  During pregnancy, the amnion (the innermost membrane surrounding the fetus) and the chorion fuse to form the amniochorionic membrane, which eventually ruptures during labor (commonly known as "water breaking"). This membrane plays a crucial role in maintaining the pregnancy and facilitating fetal growth. Full Term Placenta The full-term placenta is a discoid organ, typically 15 to 25 cm in diameter, about 3 cm thick, and weighing between 500 to 600 grams. It is structurally divided into two main surfaces: 1. Fetal Side: The fetal surface is shiny due to the presence of the amniotic membrane. This side is covered entirely by the chorionic plate, under which large arteries and veins, known as chorionic vessels, radiate from the umbilical cord towards the edges of the placenta. The umbilical cord typically attaches to the chorionic plate eccentrically but can occasionally be marginal or, rarely, insert into the chorionic membranes outside the placenta (a condition known as velamentous insertion). 2. Maternal Side: The maternal surface is dull and subdivided into 15 to 35 lobes known as cotyledons, which are slightly bulging and covered by a thin layer of decidua basalis. Grooves between the cotyledons are formed by decidual septa, which originate from the decidua basalis and extend toward the basal plate. Each cotyledon contains a main stem villus with all its branches, and the intervillous space within each lobe serves as a compartment for maternal blood circulation. At birth, the placenta detaches from the uterine wall and is expelled from the body as the afterbirth, typically about 30 minutes after the child is born. Placental Circulation The placental circulation facilitates the exchange of materials between maternal and fetal blood, vital for the growth and development of the fetus. Both the fetus and the mother contribute to this circulation, with distinct roles and structures involved. Fetal Circulation Umbilical Arteries and Vein: Poorly oxygenated blood from the fetus travels to the placenta via two umbilical arteries, which branch extensively within the chorionic plate before entering the chorionic villi. These branches form capillary networks in the terminal villi, where the exchange of gases and nutrients occurs. The oxygen-rich blood then returns to the fetus through the umbilical vein. Chorionic Villi: The chorionic villi are essential structures where this exchange happens. These villi have a large surface area, and the fetal blood is brought extremely close to the maternal blood, separated only by the thin placental membrane. The placental membrane initially consists of four layers (endothelial lining of fetal vessels, connective tissue, cytotrophoblastic layer, and syncytium) but thins out as the pregnancy progresses, increasing the efficiency of the exchange. Maternal Circulation Maternal blood enters the placenta through 80 to 100 spiral arteries, which discharge blood into the intervillous spaces. Unlike the fetal blood, maternal blood is not contained within vessels but flows freely in these intervillous spaces, forming a “lake” that bathes the chorionic villi. The blood enters the intervillous space under high pressure, which forces it deep into the space and allows it to flow slowly over the branch villi. This slow flow maximizes the exchange of oxygen and nutrients with the fetal blood. The blood eventually returns to the maternal circulation via endometrial veins. The intervillous space contains about 150 mL of maternal blood, which is replenished three to four times per minute to ensure continuous and adequate exchange. Placental Membrane The placental membrane is a structure composed of extrafetal tissues that separates the maternal and fetal blood. Initially, up to about 20 weeks of pregnancy, the placental membrane consists of four layers: 1. Syncytiotrophoblast 2. Cytotrophoblast 3. Connective tissue of the villi 4. Endothelium of fetal capillaries After 20 weeks, the cytotrophoblast in many villi becomes thinner and eventually disappears in large areas, reducing the placental membrane to three layers. In some regions, the membrane becomes so thin that the syncytiotrophoblast directly contacts the fetal capillary endothelium, forming a vasculosyncytial placental membrane.  The syncytiotrophoblast has microvilli that increase the surface area for material exchange. As pregnancy progresses, the membrane becomes thinner, bringing fetal capillary blood very close to maternal blood in the intervillous space. During the third trimester, syncytiotrophoblast nuclei aggregate to form syncytial knots, which can break off and enter the maternal circulation, where they are eventually destroyed.  The chorionic villi, with their extensive branching and microvilli on the syncytium, significantly increase the surface area for exchange. Only villi with fetal vessels in close contact with the syncytial membrane participate in this exchange.  The placental membrane (also called as a barrier) allows many substances to pass freely between maternal and fetal blood. The effectiveness of this exchange is critical for fetal health. If the maternal blood supply to the placenta is compromised, it can lead to fetal hypoxia, intrauterine growth restriction (IUGR), or even fetal death in severe cases. Function of Placenta The placenta serves several key functions crucial for fetal development, including; metabolism, transport of gases and nutrients, endocrine secretion, protection, and excretion of fetal waste products. 1. Placental Metabolism: Synthesizes glycogen, cholesterol, and fatty acids, especially during early pregnancy, to provide nutrients and energy for the fetus. 2. Placental Transfer: Gas Transfer: Oxygen, carbon dioxide, and carbon monoxide move via simple diffusion. Interruptions in oxygen transport can lead to fetal hypoxia, which is typically caused by reduced blood flow in either maternal or fetal circulation. Nutritional Transfer: Water, glucose, cholesterol, fatty acids, amino acids, and vitamins are transferred from the mother to the fetus. Water-soluble vitamins cross the placenta faster than fat-soluble vitamins. Hormones: Protein hormones (e.g., insulin) do not easily pass to the fetus, except for thyroxine and triiodothyronine. Steroid hormones, including testosterone, can pass freely, potentially affecting fetal development. Electrolytes: Freely exchanged across the placental membrane. Intravenous fluids given to the mother affect the fetal electrolyte balance. Antibodies: Maternal antibodies (IgG) provide passive immunity to the fetus against diseases like measles and diphtheria. Transferrin, a maternal protein, transfers iron to the fetus.  Waste Products: Urea, uric acid, and bilirubin are excreted by the fetus and pass through the placental membrane for clearance. Drugs and Toxins: Most drugs taken by the mother cross the placenta, potentially affecting fetal development. Drugs like heroin can lead to fetal addiction and withdrawal symptoms after birth. Medications used during labor can also affect the fetus, including respiratory depression. 3. Infectious Agents: Viruses such as rubella, cytomegalovirus, and herpes, as well as bacteria like Treponema pallidum (syphilis) and Toxoplasma gondii (toxoplasmosis), can cross the placental membrane and cause fetal infections, leading to birth defects or death. Placental Endocrine Synthesis and Secretion The placenta synthesizes both protein and steroid hormones using precursors from the fetus and mother. The key hormones produced by the syncytiotrophoblast include: Protein Hormones: 1. Human chorionic gonadotropin (hCG): - Secreted starting in the second week of pregnancy. - Maintains the corpus luteum, preventing menstruation. - Peaks at around the eighth week and then declines. 2. Human chorionic somatomammotropin (also called human placental lactogen): - Supports fetal growth and maternal metabolism. 3. Human chorionic thyrotropin: - Involved in regulating thyroid function during pregnancy. 4. Human chorionic corticotropin: - Plays a role in stress responses.  Steroid Hormones: 1. Progesterone: - Produced throughout pregnancy, essential for maintaining pregnancy. - Synthesized from maternal cholesterol or pregnenolone. - After the first trimester, the placenta takes over progesterone production, allowing the ovaries to be removed without causing abortion. 2. Estrogens: - Produced in large amounts by the syncytiotrophoblast and important for fetal development and maternal adaptations during pregnancy. Uterine Growth during Pregnancy During pregnancy, the uterus increases in size and weight to accommodate the growing conceptus (embryo and membranes), while its walls become thinner. Initially located in the pelvis, the uterus begins moving out during the first trimester. By 20 weeks, it reaches the level of the umbilicus, and by 28 to 30 weeks, it extends to the epigastric region (between the xiphoid process and the umbilicus). This growth is primarily due to hypertrophy (enlargement) of existing smooth muscle fibers, along with the development of some new fibers. Parturition Parturition is the process of childbirth, during which the fetus, placenta, and fetal membranes are expelled from the mother's reproductive tract. It involves labor, a sequence of involuntary uterine contractions that lead to the dilation of the uterine cervix and the expulsion of the fetus and placenta.  Several hormones are involved in the initiation of labor: The fetal hypothalamus secretes corticotropin-releasing hormone, which stimulates the anterior pituitary to release adrenocorticotropin, leading to the secretion of cortisol from the adrenal cortex. This is related to the production of estrogens. Oxytocin, a hormone from the pituitary gland, triggers uterine contractions and stimulates the release of prostaglandins, which increase uterine contractility. Estrogens also enhance uterine contractile activity and promote the release of oxytocin and prostaglandins. Placenta and Fetal Membranes after Birth The placenta is usually discoid in shape, measuring 15- 20 cm in diameter and 2-3 cm thick, weighing about 500-600 g, or one-sixth the weight of an average fetus. Its margins are continuous with the ruptured amniotic and chorionic sacs.  Maternal Surface The maternal surface has a cobblestone appearance, created by cotyledons separated by grooves where placental septa used to be. After delivery, parts of the decidua basalis remain in the uterus and are shed with bleeding.  Fetal Surface The umbilical cord attaches to the fetal surface, and the epithelium is continuous with the amnion, which covers the surface. The chorionic vessels branch from the umbilical cord, forming the arteriocapillary−venous system in the chorionic villi. Placental Abnormalities Placenta accreta: Abnormal adherence of chorionic villi to the myometrium. It can lead to complications when the placenta fails to detach after birth, causing hemorrhage. Placenta percreta: Villi penetrate the full thickness of the myometrium or through the perimetrium, also leading to complications and hemorrhage. Placenta previa: Occurs when the placenta implants near or over the internal os of the uterus, leading to late pregnancy bleeding and requiring cesarean delivery. Umbilical Cord The umbilical cord typically attaches near the center of the placenta but may attach in various locations, including the placental margin (battledore placenta) or the fetal membranes (velamentous insertion). It is about 1 to 2 cm in diameter and 30 to 90 cm in length (average 55 cm). The cord typically contains two arteries and one vein, surrounded by Wharton jelly. Amnion & Amniotic Fluid The amnion is a tough, fluid-filled sac that surrounds the fetus, playing a crucial role in fetal growth and development. It contains amniotic fluid, which is essential for the fetus, aiding in development, cushioning, temperature regulation, and preventing infections.  Amniotic fluid is initially secreted by the amnion and later derived from maternal tissues and fetal urine, increasing to around 700-1000 ml by the end of pregnancy. The fluid circulates as it is swallowed by the fetus and excreted through the kidneys, while water is exchanged between maternal and fetal blood. Amniotic fluid is composed of organic compounds (proteins, carbohydrates, fats) and inorganic salts, and its composition changes during pregnancy.  Studies of the fluid, obtained via amniocentesis, can help diagnose chromosomal abnormalities like Down syndrome and neural tube defects. Amniotic fluid also allows the fetus to move freely, which aids muscular development, and helps maintain homeostasis of fluid and electrolytes.  Disorders of amniotic fluid volume include: 1. Oligohydramnios (low fluid volume), often caused by placental insufficiency, kidney malformations, or urinary tract obstructions. It can lead to birth defects, such as pulmonary hypoplasia, and umbilical cord compression. 2. Polyhydramnios (excess fluid volume), often of unknown cause but sometimes related to maternal factors or fetal conditions like esophageal atresia or central nervous system defects. Ultrasonography is the primary tool for diagnosing these conditions. Preterm rupture of the amniotic sac can lead to premature labor and loss of infection protection for the fetus. Umbilical Vesicle The umbilical vesicle can be observed with ultrasound early in the fifth week. By 10 weeks, the umbilical vesicle has shrunk to a pear-shaped remnant and is connected to the midgut by a narrow omphaloenteric duct (yolk stalk). By 20 weeks, the umbilical vesicle is very small; thereafter, it is usually not visible. The presence of the amniotic sac and umbilical vesicle enables early recognition and measurement of the embryo. The umbilical vesicle is recognizable in ultrasound examinations until the end of the first trimester.  The umbilical vesicle is essential for several reasons: 1. It has a role in the transfer of nutrients to the embryo during the second and third weeks when the uteroplacental circulation is being established. 2. Blood cell development first occurs in the well vascularized extraembryonic mesoderm covering the wall of the umbilical vesicle beginning in the third week and continues to form there until hemopoietic activity begins in the liver during the sixth week. 3. During the fourth week, the endoderm of the umbilical vesicle is incorporated into the embryo as the primordial gut. 4. Primordial germ cells appear in the endodermal lining of the wall of the umbilical vesicle in the third week and subsequently migrate to the developing gonads.  It atrophies as pregnancy advances, eventually becoming very small. In very unusual cases, the umbilical vesicle persists throughout pregnancy and appears under the amnion as a small structure on the fetal surface of the placenta near the attachment of the umbilical cord. The omphaloenteric duct usually detaches from the midgut loop by the end of the sixth week. In approximately 2% of adults, the proximal intra-abdominal part of the omphaloenteric duct persists as an ileal diverticulum (Meckel diverticulum). Allantois In the third week, it appears as a sausage-like diverticulum from the caudal wall of the umbilical vesicle that extends into the connecting stalk. During the second month, the extraembryonic part of the allantois degenerates.  Although the allantois is not functional in human embryos, it is important for three reasons: 1. Blood cell formation occurs in its wall during the third to fifth weeks. 2. Its blood vessels persist as the umbilical vein and arteries. 3. The intraembryonic part of the allantois passes from the umbilicus to the urinary bladder, with which it is continuous. As the bladder enlarges, the allantois involutes to form a thick tube, the urachus. After birth, the urachus becomes a fibrous cord, the median umbilical ligament, which extends from the apex of the urinary bladder to the umbilicus. Multiple Pregnancies Multiple Pregnancies carry higher risks of chromosomal anomalies, fetal morbidity, and mortality compared to single pregnancies, with increased risks as the number of fetuses rises. The rise in multiple births is linked to fertility treatments and ovulation induction. Types of Twins 1. Dizygotic (DZ) Twins: Also called fraternal twins, they originate from two zygotes, resulting in two distinct individuals, which may be of the same or different sexes. DZ twins always have two amnions and two chorions, but their placentas may fuse. The incidence of DZ twinning is influenced by hereditary and racial factors, with a higher frequency in certain populations (e.g., 1 in 20 in some African populations). 2. Monozygotic (MZ) Twins: Also known as identical twins, they originate from a single zygote, splitting into two embryos. They are genetically identical and always of the same sex. MZ twinning typically occurs during the blastocyst stage, often resulting in two amniotic sacs but one shared chorionic sac and placenta. Rarely, early separation of blastomeres may lead to MZ twins with separate placentas and membranes, making them indistinguishable from DZ twins based on placental structure alone. 3. Other Types of Multiple Births: Triplets and higher multiples can arise from one, two, or three zygotes. The combinations can involve identical and non-identical individuals. Conjoined twins result from incomplete division or fusion of embryonic discs. They are named according to the region of attachment (e.g., thoracopagus for chest fusion). The incidence is rare (1 in 50,000 to 100,000 births), and separation is often challenging or not viable. Superfecundation & Superfetation: Superfecundation refers to the fertilization of two or more oocytes at different times, potentially leading to twins with different fathers. Superfetation, where fetuses are conceived at different times, is extremely rare in humans.