Placentation - Rod D. Braun (PDF)

Placentation Rod D. Braun Page 1 of 34 PLACENTATION Lecture Learning Objectives: 1. Describe the formation of the primitive placenta. Describe the fo...

Placentation Rod D. Braun Page 1 of 34 PLACENTATION Lecture Learning Objectives: 1. Describe the formation of the primitive placenta. Describe the formation of lacunar blood network. Describe the formation of chorionic villi. Describe the formation of the primitive placenta. 2. Describe the development of the early placenta. Describe the decidua during the first trimester. Compare and contrast the three regions of the decidua. Describe the chorion during the first trimester. Compare and contrast the two regions of the chorion. Describe the structure of the placenta at the end of the first trimester. 3. Describe the organization and structure of the placenta. Describe the fetal portion of the placenta, the villous chorion. Describe the maternal portion of the placenta, the decidua basalis. 4. Describe the interaction of the chorionic villi with the intervillous space and the basal plate. Describe chorionic villi. Describe the changes in chorionic villi structure during gestation. Describe the placental barrier, site of exchange between maternal and fetal circulation. Describe the components of the basal plate. Describe anchoring villi. Describe extravillous trophoblasts. Describe the role of extravillous trophoblasts in placental structure and pathophysiology. Describe the maternal-fetal circulation of the placenta. Describe how the placental barrier is crossed by gases, nutrients, waste, antibodies, and drugs. Describe the endocrine functions of the placenta. 5. Describe the structure and function of the amniotic cavity. Describe the structure and function of the amniochorionic membrane. Describe the source(s) of amniotic fluid and its flow in the fetus. Describe the functions of amniotic fluid. Describe the consequences of problems with amniotic fluid balance. Describe oligohydramnios, including its cause. Describe polyhydramnios, including its cause. 6. Describe the appearance of the term placenta, i.e., the placenta upon delivery. Placentation Rod D. Braun Page 2 of 34 7. Describe the placenta and membranes of twins. Describe the placenta of dizygotic twins. Describe the placenta of monozygotic twins. Describe the placenta of monozygotic twins that separate before blastocyst formation. Describe the placenta of monozygotic twins that separate during blastocyst formation. Describe the placenta of monozygotic twins that separate after implantation. Lecture Content Outline I. Review of the Primitive Placenta A. Formation of Lacunar Blood Network B. Formation of Chorionic Villi C. Formation of Primitive Placenta II. Development of Early Placenta A. Decidua during the First Trimester B. Chorion during the First Trimester C. Placenta at the End of the First Trimester III. Organization and Structure of the Placenta A. Fetal Portion: Villous Chorion (Chorion Frondosum) B. Maternal Portion: Decidua Basalis IV. Chorionic Villi and Placental Function A. Chorionic Villi (floating or branching villi) B. Basal Plate and Anchoring Villi C. Extravillous Trophoblasts D. Placental Circulation E. Placental Transport F. Endocrine Functions of the Placenta V. Amniotic Cavity A. Amniochorionic Membrane B. Amniotic Fluid C. Functions of Amniotic Fluid D. Problems with Amniotic Fluid Balance VI. Term Placenta A. Placenta at birth B. Appearance of term placenta VII. Placenta and Membranes of Twins A. Dizygotic Twins (non-identical twins) B. Monozygotic Twins (Identical Twins) Placentation Rod D. Braun Page 3 of 34 PLACENTATION I. REVIEW OF THE PRIMITIVE PLACENTA Mammalian embryos, unlike most other vertebrate embryos, require an external source of nutrients to grow and develop. The embryo accomplishes this by establishing a communication with the maternal blood supply leading to formation of the placenta. Details on the formation of the primitive placenta were presented in the “Bilaminar Embryo: Week 2” lecture in the Figure 1. Formation of trophoblastic lacunae within the “Foundations” Unit, but it will be syncytiotrophoblast, while the exocoelomic (Heuser’s) membrane lining the primary yolk sac is simultaneously being reviewed here. formed (~day 9). Modified from Figure 2-3 from Larsen’s th Human Embryology (Schoenwolf et al., 5 ed., 2015). A. Formation of lacunar blood network 1. While the primary yolk sac is forming (~days 9- 10), the syncytiotrophoblast forms small internal cavities called trophoblastic lacunae that anastomose to create a lacunar network within the Figure 2. Maternal blood filling the network of trophoblastic lacunae and primary stem villi forming from the cytrotrophoblast, syncytiotrophoblast while the extraembryonic mesoderm is simultaneously being formed (~days 10-11). Modified from Figure 2-4A in Larsen’s (~day 9, Figure 1). th Human Embryology (Schoenwolf et al., 5 ed., 2015). Placentation Rod D. Braun Page 4 of 34 2. Invading syncytiotrophoblast also begins to engulf maternal endometrial capillaries and maternal blood fills the network of trophoblastic lacunae (days 10-11, Figure 2). B. Formation of chorionic villi 1. Formation of primary stem villi a. Focal regions of cytotrophoblast begin to proliferate and form cellular columnar structures that protrude into syncytiotrophoblast. b. These cellular columns of cytotrophoblast surrounded by syncytiotrophoblast are called primary chorionic stem villi (~days 10-11, Figure 2, “developing primary villus”). c. As the lacunar network and primary stem villi continue to grow and expand, the lacunar blood comes into increased contact with the primary stem villi (~days Figure 3. Presence of primary chorionic stem villi in contact with 12-13, Figure 3, maternal blood in the trophoblastic lacunar network (~days 12- 13). Modified from Figure 2-5B in Larsen’s Human Embryology “primary villus”). th (Schoenwolf et al., 5 ed., 2015). d. Primary stem villus consists of a core of cytotrophoblast surrounded by syncytiotrophoblast (Figure 4, left). Placentation Rod D. Braun Page 5 of 34 Figure 4. Chorionic stem villi during development: primary (left), secondary (center), and tertiary (right). Adapted from Figure 2-8 th in Larsen’s Human Embryology (Schoenwolf et al., 5 ed., 2015). 2. Formation of secondary stem villi (~days 15-17): Underlying extraembryonic somatopleuric mesoderm moves up into the center of a primary stem villus, forming the core of a secondary stem villus Figure 5. Presence of secondary chorionic stem villi in contact (Figures 4 and 5). with maternal blood in the trophoblastic lacunar network (days15). Modified from Figure 2-6 in Larsen’s Human th Embryology (Schoenwolf et al., 5 ed., 2015). 3. Formation of tertiary stem villi (day 21) a. Some mesenchymal cells in the core of extraembryonic somatopleuric mesoderm in the stem villus form blood islands and differentiate into capillaries and blood cells (Figure 4, right). b. The capillaries in the tertiary chorionic stem villi fuse to form arteriocapillary networks (Figure 4, right). Placentation Rod D. Braun Page 6 of 34 C. Formation of the primitive placenta 1. The villous arteriocapillary networks soon become connected with the embryonic heart through vessels in the extraembryonic somatopleuric Decidua mesoderm of the chorion and Figure 6. Diagram of a sagittal section of an embryo (week 4), showing the primitive placenta. Figure 4-14C from The connecting stalk Developing Human: Clinically Oriented Embryology (Moore et th al., 10 ed., 2016). (Figures 5 and 6). 2. Embryonic blood begins to flow slowly through the capillaries in the tertiary chorionic stem villi by the end of week 3, establishing the primitive placenta (Figure 6). 3. The primitive placenta has a maternal component and an embryonic (fetal) component (Figure 6): a. The maternal component consists of the decidua. Recall that the region of the uterine endometrium at the site of implantation is called the decidua. i. Decidua: Differentiated endometrium of the uterus. ii. Endometrial fibroblasts have developed into decidual cells that support the developing placenta. b. The embryonic (fetal) component consists of the chorion with the developing chorionic villi. Placentation Rod D. Braun Page 7 of 34 Figure 7. Left: Diagram of a sagittal section of an implanted embryo (week 4) within the uterine endometrium (decidua). Modified from Figure 7.10A in Sadler, TW, Langman’s th Medical Embryology, 11 ed., 2010. Right: Diagram of the implanted embryo (week 4) within the endometrium (decidua), showing the primitive placenta. Figure 4-14C from The Developing Human: Clinically Oriented Embryology (Moore et al., th 10 ed., 2016). 4. At this stage (~week 4), the embryo, amniotic cavity, and chorionic cavity have not yet significantly expanded out into the uterine cavity (Figure 7). Figure 8. Growth of embryo, amniotic cavity, and chorionic nd cavity during 2 month of development. Note that the embryo and the cavities have grown and extended out into the uterine cavity. Modified rom Figure 7.10A in Sadler, TW, Langman’s Medical Embryology, th 11 ed., 2010. II. DEVELOPMENT OF EARLY PLACENTA During the first trimester, the growth of the embryo and amniotic cavity result in some changes in the decidua and the chorion. A. Decidua during the first trimester 1. After formation of the primitive placenta, the embryo and amniotic cavity continue to grow, and they grow so much that they soon extend out into the cavity of the uterus (Figure 8). Placentation Rod D. Braun Page 8 of 34 2. As the embryo and cavities grow, three regions of the decidua can be distinguished (Figures 7 and 8): a. Decidua Basalis i. Decidua (differentiated endometrium) directly beneath the conceptus. ii. Comprises the maternal portion of the placenta. iii. Forms the basal plate (floor) of the placenta. b. Decidua Capsularis: Decidua directly overlying the implanted conceptus. c. Decidua Parietalis: The remainder of the endometrium not directly in contact with the conceptus. Figure 9. Left: Diagram of a sagittal section of an implanted embryo (week 4) within the uterine endometrium (decidua). Modified from Figure 7.10A in Sadler, TW, Langman’s Medical th Embryology, 11 ed., 2010. Right: Diagram of the implanted embryo (~weeks 4-5) within the endometrium (decidua), showing only the fetal portion of the primitive placenta. Note that the primitive placenta extends all around the chorionic cavity. Modified from Figure 7-20B.in The Developing Human: Clinically Oriented Embryology (Moore et th al., 10 ed., 2016). B. Chorion during the first trimester 1. From the formation of the primitive placenta in week 3 until week 8, the entire chorion is covered by tertiary chorionic villi (Figure 9). Placentation Rod D. Braun Page 9 of 34 2. As the embryo and amniotic cavity continue to grow during the first trimester, the chorionic villi bordering the decidua capsularis are stretched by growth and compressed until they lose their blood supply (Figure 10). Figure 10. Left: Diagram of a sagittal section of a developing embryo (~2 months). Figure 7.10A in Sadler, TW, Langman’s Medical th Embryology, 11 ed., 2010. Right: Developing fetus, amniotic cavity, chorionic cavity, and primitive placenta at week 10. Note that the primitive placenta bordering the decidua capsularis has begun to degenerate, forming the smooth chorion (chorion leave). The chorion with tertiary villi is called the villous chorion (chorion frondosum). Modified from Figure 7-20C in The Developing Human: Clinically Oriented Embryology (Moore et al., th 10 ed., 2016). 3. At this stage, there are two parts to the chorion (Figure 10): a. Villous chorion (chorion frondosum) i. Portion of the chorion that still contains tertiary villi in contact with the decidua basalis. ii. The villous chorion forms the fetal side of the placenta. b. Smooth chorion (chorion laeve) i. Portion of the chorion where villi and vasculature are lost. ii. The chorion laeve contains avascular mesoderm. iii. The smooth chorion is in contact with the decidua capsularis. Placentation Rod D. Braun Page 10 of 34 Figure 11. Left: Diagram of a sagittal section of a developing fetus (~3 months). Figure 7.10B in Sadler, TW, Langman’s th Medical Embryology, 11 ed., 2010. Right: Developing fetus, amniotic cavity, and placenta at week 20. Note that portion of the chorion that has become smooth chorion (chorion leave) has increased. The villous chorion (chorion frondosum) will form the fetal portion of the true placenta. Modified from Figure 7-20D in The Developing Human: Clinically Oriented Embryology th (Moore et al., 10 ed., 2016). C. Placenta at the end of the first trimester (Figure 11) 1. The fetus and amniotic cavity continue to grow rapidly, and by the end of the third month: a. The amniotic cavity continues to grow out into the uterine cavity and fills up most of the uterine cavity. b. Chorion at end of first trimester i. The amnion comes in contact with smooth chorion, obliterating the chorionic cavity. ii. The smooth chorion (chorion laeve) stretches over the expanded amnion. iii. Most of chorion is smooth chorion. c. Decidua at end of first trimester i. The decidua capsularis is pushed toward the decidua parietalis. ii. The decidua capsularis degenerates, leaving only decidua parietalis and decidua basalis. iii. The decidua parietalis, chorion leave, and amnion form a fused layer. Placentation Rod D. Braun Page 11 of 34 2. The true placenta is formed by the remaining portions of the primitive placenta: a. Fetal portion: the villous chorion b. Maternal portion: the decidua basalis Figure 12. Left: Diagram of a sagittal section of a developing fetus (~3 months). The boxed area identifies the placenta, which is shown in greater detail on the right. Figure 7.10B in Sadler, TW, Langman’s Medical Embryology, 11th ed., 2010. Right: Schematic drawing of a transverse section through a fully developed placenta. Note the two umbilical arteries and the single umbilical vein in the umbilical cord. The boxed region is shown in more detail in Figure 13. Figure 7-5 in The Developing Human: Clinically Oriented th Embryology (Moore et al., 10 ed., 2016). III. ORGANIZATION AND STRUCTURE OF THE PLACENTA At birth, the placenta has the appearance of a flattened disc. It is 2-3 cm thick and 15-20 cm across. It weighs 500-600 grams. The placenta is a fetomaternal organ and has a fetal portion and a maternal portion (Figure 12). The fetal portion is the villous chorion (chorion frondosum), which consists of the chorionic plate and the chorionic villi. The maternal portion is the decidual basalis. A. Fetal portion: Villous Chorion (Chorion Frondosum) 1. Villous chorion consists of chorionic plate and chorionic villi (Figures 12 and 13). a. The chorionic plate is called the "roof" of the placenta (Figure 12). Placentation Rod D. Braun Page 12 of 34 b. Structure of chorionic plate (Figures 12 and 13) i. Vascularized extraembryonic somatopleuric mesoderm continuous with umbilical cord (Figures 12 and 13). Figure 13. Schematic drawing of a transverse section through a portion of a fully developed placenta, showing the basics of placental structure. This is the boxed region indicated in the right panel of Figure 12. The fetal portion consists of the chorionic plate and the chorionic villi. The maternal portion consists of the decidua basalis at the bottom of the diagram. Figure 2.15 in Netter's Atlas of Human Embryology (Cochard, Updated Edition, 2012). ii. Underside of chorionic plate is lined with an inner layer of cytotrophoblast and an outer layer of syncytiotrophoblast (continuous with the chorionic villi) (Figure 13). iii. Amnion tightly apposes the extraembryonic somatopleuric mesoderm of the chorionic plate (Figure 13). iv. Blood vessels from umbilical cord branch out across the chorionic plate to feed the main stem villi (Figures 12 and 13). Placentation Rod D. Braun Page 13 of 34 c. Chorionic villi (Figures 12 and 13) i. Main stem villi emerge from the underside of the chorionic plate and repeatedly branch into smaller and smaller chorionic villi. ii. Core of villi contains extraembryonic somatopleuric mesoderm, continuous with the mesoderm of the chorionic plate. iii. Villi are lined by an inner layer of cytotrophoblast and an outer layer of syncytiotrophoblast that are continuous with the same layers in the chorionic plate (Figure 13). iv. Villi contain fetal capillaries that connect to larger vessels in the chorionic plate, which in turn are connected to the umbilical vessels. 2. The villous chorion is continuous with the umbilical cord. a. Umbilical cord is a roughly 50 cm-long cord that attaches the fetus to the placenta. b. The mature umbilical cord (Figures 13 and 14) is composed of: i. An outermost layer of amnion (epithelial layer of amnioblasts). ii. A mucoid mesoderm (Wharton's jelly) Placentation Rod D. Braun Page 14 of 34 iii. One umbilical vein: brings relatively well- oxygenated blood from the placenta back to the fetal heart. Figure 14. Section through an umbilical cord, showing the amnion covering, the mucoid center of Wharton’s iv. Two umbilical jelly, two umbilical arteries, and an umbilical vein. arteries: bring relatively deoxygenated fetal blood from the fetal heart to the placenta. B. Maternal portion: Decidua Basalis 1. The maternal portion of the placenta is the decidua basalis, which is the differentiated endometrium of the uterus underlying the site of implantation. 2. Structure of the decidua basalis (Figures 12 and 13) a. Endometrial fibroblasts have developed into decidual cells that support the placenta. b. Maternal endometrial veins and arteries are found in the decidua basalis. i. The endometrial arteries coil and become spiral arteries. ii. Spiral arteries deliver oxygen-rich maternal, arterial blood into the intervillous space that surrounds the chorionic villi and bathes them in maternal blood. Placentation Rod D. Braun Page 15 of 34 c. The decidua basalis extends placental (decidual) septa into the intervillous space that divides the placenta into 10-25 lobules or cotyledons (Figures 12 and 13). 3. The decidua basalis forms part of the basal plate. a. The basal plate is the “floor” of the placenta. b. It is the site where the fetal components of the placenta meet the maternal components of the placenta c. The basal plate is composed of the decidua basalis and fetal cytotrophoblast (cytotrophoblastic shell) (Figure 13). 4. The decidua basalis is shed at parturition with the rest of the placenta. IV. CHORIONIC VILLI AND PLACENTAL FUNCTION A. Chorionic Villi (floating or branching villi) 1. Villi are bathed in maternal blood of the intervillous space (Figures 12, 13, and 15). 2. Anchoring villi form where chorionic villi contact the basal plate of the placenta (Figures 12, 13, and 15). 3. Branching of the chorionic villi increases during gestation (compare left and right panels of Figure 15). Placentation Rod D. Braun Page 16 of 34 Figure 5. Diagrams showing the developing placenta in the first trimester (left) and second trimester (i h) Figure 15. Diagram showing the developing placenta during the first trimester (left) and second trimester (right). 4. Changes in chorionic villi during pregnancy: As the fetus grows, exchange across the placenta is enhanced by two factors: a. Increased villous surface area (due to branching) (Figure 15). b. A thinner "placental barrier" (fewer cell layers separate maternal blood from fetal blood) (Figure 16). Figure 16. Change in placental barrier across the chorionic villi during pregnancy. Left: Cross-section of st chorionic villus during 1 trimester. Right: Cross-section of chorionic villus nd during 2 trimester. From Figure 8.8- C and 8.8-D in Sadler, TW, th Langman’s Medical Embryology, 11 ed., 2010. 5. Placental Barrier (Figure 16) a. Placental barrier separates the intervillous space, filled with maternal blood, from the fetal capillary lumen in the villus, filled with fetal blood. Placentation Rod D. Braun Page 17 of 34 b. Components of placental barrier (from intervillous space inward) during early gestation, i.e., during 1st trimester (Figure 16, left): i. Syncytiotrophoblast (syncytium) ii. Cytotrophoblast cell iii. Mesenchyme (connective tissue) iv. Capillary endothelial cell c. As the placenta matures and the chorionic villi continue to branch, the placental barrier becomes thinner. Later in gestation, i.e., during 2nd trimester, the following changes occur (Figure 16, right): i. Fetal capillaries form at periphery of villi. ii. Fewer cytotrophoblasts remain as cells fuse into syncytiotrophoblast. iii. Loss of cytotrophoblasts causes a thinning of "placental barrier". iv. The components of placental barrier (from intervillous space inward) are now only the syncytiotrophoblast (syncytium) and the capillary endothelial cell (Figure 16, right). B. Basal Plate and Anchoring Villi 1. The basal plate is the “floor” of the placenta and is composed of the decidua basalis and a cytotrophoblastic shell of fetal cytotrophoblasts (Figure 13). Placentation Rod D. Braun Page 18 of 34 2. Anchoring villi a. Anchoring villi are chorionic villi (fetal origin) that contact and anchor down to the decidua basalis (Figure 13). b. Anchoring villi form columns of highly proliferating cytotrophoblast cells (Figure 17). c. Dense packing of columns appears as cytotrophoblastic shell (Figures 13 and 17). Figure 17. Schematic showing columns of proliferating cytotrophoblast cells in an anchoring villus (top). Some of these cells break away from the columns and invade the decidua basalis as extravillous trophoblasts (here labeled invasive cytotrophoblasts, iCTB). The extravillous cytotrophoblasts invade the decidua and remodel uterine arteries. They eventually invade about 1/3 of way into myometrium (bottom). AV: anchoring villus, CCT: cell column trophoblast, EC: vascular endothelial cell, eCTB: endovascular trophoblast, iCTB: interstitial cytotrophoblast, Mφ: macrophage, SA: spiral artery, SMC: smooth muscle cell; ST: syncytiotrophoblast, vCTB: villous cytotropholast. Modified from Figure 1 in Pollheimer et al. (Placenta, 35 Suppl: S57-S63, 2014). C. Extravillous Trophoblasts (Figure 17) 1. Cytotrophoblasts break away from columns of cytotrophobalstic shell to colonize the decidua basalis. 2. Invading cytotrophoblasts are called extravillous trophoblast cells (iCTB or interstitial cytotrophoblast in Figure 17). 3. They invade the decidua basalis and remodel the uterine tissues and uterine vasculature. Placentation Rod D. Braun Page 19 of 34 4. Extravillous trophoblasts can be identified in decidua by expression of cytokeratin-7 (Figure 18). Only cells derived from epithelium make cytokeratin type 7 (CK7; i.e., all trophoblasts). Figure 18. Left: H&E-stained light micrograph (LM) showing basal plate with maternal blood vessels (lower right corner of section), anchoring villi and free (floating) villi. Intervillous space filled with maternal blood is toward top. Right: Adjacent section stained with antibody to cytokeratin 7 to show cytotrophoblast cells (stained brown), which are of epithelial origin, hence their staining for cytokeratins. Note that the core of the villi and the decidual cells of the basal plate, both of mesenchymal origin, do not stain. Extravillous cytotrophoblast cells have invaded the decidua and some have even invaded the maternal blood vessels (lower right). 5. Importantly, the extravillous trophoblasts invade maternal spiral arteries, penetrating as far as the upper third of the myometrium (Figures 17 and 18). a. Trophoblasts break down the vascular smooth muscle and displace the endothelial cells that line the arteries (Figures 17 and 18). b. Remodeled blood vessels lose tone and remain dilated. c. These vessels can transport an increased blood volume to the intervillous space due to their high capacity and low resistance (Figure 19). Placentation Rod D. Braun Page 20 of 34 Figure 19. Remodeling of spiral arteries by extravillous trophoblasts. Left: Schematic showing spiral arteries toward end of first trimester, when remodeling of spiral arteries by extravillous trophoblasts is beginning. Trophoblast cells invade from the columns into spiral arteries, replacing smooth muscle and endothelial cells. Left: As remodeling continues in second trimester, blood vessels become low resistance conduits of maternal blood into the intervillous space, and blood flow increases. Modified from Figure 1D in Carter, AM (Physiological Reviews, 92(4):1543-1576, 2012). 6. Preeclampsia a. Poor extravillous trophoblast survival and invasion (Figure 20) may contribute to the pregnancy disorder, Figure 20. Sections of placenta from a normal patient (left) preeclampsia. and from a patient with preeclampsia (right). Both sections were stained for cytokeratin-7 to label trophoblasts. Direction of decidual invasion by extravillous trophoblasts is indicated by the arrows. Note the poor invasion of the decidua basalis b. Poor trophoblast by extravillous trophoblasts on the right. invasion leads to: i. No physiologic conversion of spiral arteries (Figure 21). ii. Poor blood flow to intervillous space. Placentation Rod D. Braun Page 21 of 34 Figure 21. H&E-stained sections from deep in the placental bed of a normal patient (left) and of a patient with preeclampsia (right), showing the spiral arteries. Both sections are shown at the same magnification. Note the remodeled spiral artery in the normal placenta on the left. The spiral arteries in the patient with preeclampsia are small, round and constricted. They have relatively thick, muscular tunica medias, typical of arteries. c. Because blood flow to the placenta is poor, the mother's circulatory system compensates by increasing blood pressure. d. Hypertension and kidney dysfunction (proteinuria) produced during preeclampsia puts both mother and fetus at risk, often forcing doctors to terminate pregnancy in the second or early third trimester. e. Removal of the placenta completely eliminates all symptoms of (cures) preeclampsia. f. Significant morbidity and mortality i. Affects 5-7% of all pregnancies. ii. Accounts for 40-80% of maternal deaths. iii. Accounts for a large number (15%) of premature births. Placentation Rod D. Braun Page 22 of 34 Figure 22. Schematic drawing of a transverse section through a fully developed placenta. Note the two umbilical arteries and the single umbilical vein in the umbilical cord, which form the fetal side of the placental circulation. The maternal side of the placental circulation consists of the endometrial (uterine) arteries and veins. The endometrial arteries supply blood to the spiral arteries in the decidua basalis, which in turn deliver oxygenated maternal blood to the intervillous space. The blood is drained by the endometrial (uterine) veins. Figure 7-5 in The Developing Human: Clinically Oriented th Embryology (Moore et al., 10 ed., 2016). D. Placental Circulation 1. Placental circulation includes both a maternal and fetal component (Figure 22). 2. Maternal circulation a. Endometrial (uterine) arteries supply maternal arterial blood to the spiral uterine arteries. b. Spiral uterine arteries (modified by extravillous cytotrophoblasts) empty through the placental floor and supply oxygenated maternal blood to the intervillous space. c. Maternal blood flows through the intervillous space toward the roof of the placenta and returns, bathing the chorionic villi, toward the floor of the placenta. d. Deoxygenated blood is drained by uterine veins. Placentation Rod D. Braun Page 23 of 34 3. Fetal circulation a. Deoxygenated blood from fetus through two umbilical arteries to placenta. b. Oxygenated fetal blood returns through venules in the villi to veins that connect to the umbilical vein. 4. Exchange takes place between fetal capillaries in the chorionic villi and maternal blood in the intervillous space across the placental barrier. E. Placental Transport (Figure 26) 1. Transport of Gases a. O2 and CO2 diffuse freely across partial pressure gradients (high to low). b. O2 partial pressure (pO2) gradient i. Maternal blood at pO2 of 50 mm Hg. ii. Fetal blood in villi at only 30 mm Hg. iii. 20 mm Hg partial pressure gradient across placental membrane iv. Since maternal pO2 is higher, oxygen diffuses toward fetal blood. 2. Nutrients: most cross freely. 3. Waste products cross freely: CO2, urea, uric acid, bilirubin, creatinine Placentation Rod D. Braun Page 24 of 34 Figure 23. Diagram showing transport across the placental barrier. Modified from Figure 7-7 from The Developing Human: th Clinically Oriented Embryology (Moore et al., 10 ed., 2016). 4. Antibodies: IgG, but not other immunoglobulin classes. Confers passive immunity to fetus 5. Drugs: Most cross by simple diffusion. F. Endocrine Functions of the Placenta (Figure 24) 1. Hormones are secreted into maternal blood by the syncytiotrophoblast. 2. Syncytiotrophoblast produces human chorionic gonadotropin (hCG) Figure 24. Diagram of a transverse section through a chorionic villus, showing production of a. hCG maintains corpus luteum in hormones by syncytiotrophoblast. From Figure 5.11C in Sadler, TW, Langman’s Medical the first trimester. th Embryology, 12 ed., 2011. Placentation Rod D. Braun Page 25 of 34 b. Corpus luteum is the major source of progesterone and estrogens early in pregnancy. 3. Syncytiotrophoblast produces human placental lactogen (hPL). 4. After 8 weeks of gestation, the placenta emerges as the major source of progesterone and estrogens; however, it cannot synthesize these hormones by itself. a. The placenta requires the assistance of both mother and fetus: the “maternal-placental-fetal unit”. b. The “maternal-placental-fetal unit” will be discussed by Dr. Gomez-Lopez in the “Pregnancy and Parturition” lecture. V. AMNIOTIC CAVITY A. Amniochorionic Membrane 1. Recall that during the first trimester, the amniotic cavity continues to grow. a. Amniotic cavity is filled with Figure 25. Development of the placenta from the end of the 2nd month (left) to the end of the 3rd month (right). By the end amniotic fluid. of the third month, the amnion and chorion have fused, and the decidua capsularis has degenerated. Figure 7.10 from Sadler, th TW, Langman’s Medical Embryology, 11 ed., 2010. b. As the amniotic cavity grows, the chorionic cavity is displaced and the two membranes (amnion and chorion laeve) become closely apposed (Figure 25, right), forming the amniochorionic membrane (Figure 26). Placentation Rod D. Braun Page 26 of 34 2. Preterm rupturing of the amniochorionic membrane is the leading cause of premature births. 3. The amnion contributes most of the strength to the barrier that contains the amniotic fluid. B. Amniotic Fluid 1. Amniotic fluid fills the amniotic cavity, which is surrounded by the amniochorionic membrane (amnion + chorion laeve). Figure 26. Top: Image of a fetus suspended in the amniotic cavity, 2. Volume up to 1000 cc showing the placenta, amniotic membrane, and chorionic membrane. The box indicates the location of the histological H&E- at birth. stained section shown in the bottom panel. Bottom: H&E-stained section showing the amniochorionic membrane. This section is from the region indicated by the box in the top panel. 3. Fluid is formed from water in maternal and fetal circulation. a. Fluid is exchanged between decidua parietalis and amniotic cavity across amniochorionic membrane. b. Later in development fluid is exchanged between intervillous blood and amniotic cavity across the chorionic plate. Placentation Rod D. Braun Page 27 of 34 4. Fetus swallows and excretes amniotic fluid (Figure 27). a. Fetus swallows amniotic fluid. i. Fluid is absorbed in the fetal digestive tract. ii. The fluid passes into the Figure 27. Diagram showing exchange of fluid between fetal the amniotic cavity and the roof of the placenta (chorionic plate on right). Also shown is fluid exchange between the amniotic cavity and the fetus. bloodstream. iii. The fetal blood is carried to the chorionic villi by the umbilical arteries. iv. Water and waste products in the blood cross the placental barrier (membrane) and enter maternal blood in the intervillous space. b. Excess water in the fetal blood is excreted by fetal kidneys as urine into the amniotic cavity. After about 16 weeks, fetal urine makes an important contribution to the amniotic fluid. C. Functions of Amniotic Fluid 1. It functions in protecting the fetus. a. Prevents adhesion of amnion to embryo. Placentation Rod D. Braun Page 28 of 34 b. Cushions against impacts to mother. c. Controls body temperature of fetus. d. Provides protection against infection. 2. Permits fetal movement, aiding musculoskeletal development. 3. Buoyant medium for symmetrical growth of fetus. D. Problems with Amniotic Fluid Balance 1. Oligohydramnios a. Reduced amniotic fluid (