Normal Anatomy – membranes completely surround the placenta and fill up the uterus

• formed by:
• (1) Chorion – fetal portion, composed of syncytiotrophoblast, cytotrophoblast, extraembrionic somatic mesoderm
• form villi structures that allow for exchange between fetal and maternal blood:
• primary chorionic villi – no gas exchange, like bronchi in lung, just transporting blood
• secondary/tertiary villi – gas exchange occurs here; problem here can affect the fetus; capillaries surrounded by trophoblast form the spaces where maternal blood flows
• Chorionic Plate – layer of placenta from which villi project
• Histology: thick connective tissue (collagen) and thick walled vessel with baby’s blood
• (2) Decidua basalis – maternal portion: portion of endometrium that underlies implantation site
• Basal plate: compact layer made of deciduized endometrium, spiral arteries, gravid myometrium, invading trophoblast
• Histology: trophoblast are dark purple cells that anchor the placenta to the uterus at interface with villi
• trophoblast separated from maternal endometrium by a lot of fibrin; pink fibrinoid material = villi
• arteries bring maternal blood into placenta but are not likely to be seen in a random sample
• overall an indistinct structure without a lot of connective tissue or arteries.
• intervillous space–lined by trophoblast (which surround villi) and filled with maternal blood; where gas exchange occurs
• (3) Membranes – smooth part of placenta that surrounds fetus and blends into the discoid portion that contains villi
• have a chorionic plate, a basal plate, and villi; no fetal vessels; intervillous space collapsed – only trophoblast left
• placenta thus fills entire uterus
• Additional Anatomy:
• Umbilical cord – connects placenta to baby by means of 2 fetal arteries and 1 vein
• vessels suspended in Wharton’s Jelly (glycosaminoglycan with thixotropic propertiesÞ resists compression and occlusion)
• often cord can wrap around body parts; rarely ties in knot Þ fetal death (chance occurrence)
• Amniotic sac – fetal epithelial-lined sac containing mainly fetal urine (amniotic fluid)

• Fetal side: deoxygenated baby blood returns to placenta via paired anastomosing umbilical arteries (only need one)
• arteries enter chorionic plate sending branches into the villi until becoming capillaries in the terminal villi
• gas exchange occurs at the terminal villi Þ blood drains into one large, thin-walled umbilical vein (occlusion a problem)
• Maternal side: mother’s blood surrounds villous tree like a bathtub into which 80-100 transformed arteries drain
• blood then exits through veins

• origin of the placenta; pre-germ cell layer epithelium arising in parallel with the inner cell mass
• in early blastocyst stage a few cells form inside which form the embryo; the rest (outside) Þ trophoblast Þ placenta
• form a continuous cellular envelope that separates the fetus from the mother at every level
• Functions of Trophoblast
• barrier: tight junctions protect the fetus from microorganisms and immune attack (lack transplant anitgens)
• angioinvasion: implants embryo into uterus by eroding and remodeling maternal vessels
• endocrine: hundreds of hormones released, only a few understood: estrogen, progesterone, hCG, hLP, etc.
• transport: passive, facilitated and active transport of gases, ions, metabolic substrates and selected macromolecules (including drugs) from mother to fetus
• Genomic Imprinting (distinct from fetus)
• Maternal genome critical for fetal development (random inactivation of maternal and paternal X chromosomes)
• no maternal genesÞ hydatidiform mole–egg without female pro-nucleus fertilized by single sperm which reduplicates Þ placental development with little fetal development
• Histology: grape-like clusters of villi; trophoblast proliferates out of control, which fills villi with H₂O
• form of gestational trophoblastic disease – precursor for malignant tumors of the placenta = coriocarcinoma
• very responsive to chemo-therapy
• Paternal genome critical for placental development (inactivation of paternal X chromosome)
• no paternal genes Þ teratoma–develops from germ cell in ovary Þ Ý Ý fetal tissue/no placenta
• Histology: repirstory epithelium, cartilage, mesoderm, various epithelial lineages; no trophoblasts
• Trophoblast Subtypes – trophectoderm stem cells from the outside of the blastocyst
• intermediate (invasive) Trophoblast – in the basal plate of the placenta forming a shell that invades the uterus
• invades the maternal blood vessels to gain blood supply for the placenta then differentiates into a giant cell
• villus cytotrophoblast – exchanging cells that form around the outside of the villi
• villus syncytiotrophoblast – derived from cytotrophoblast; cells fuse into a syncytium (multiple nuclei) that forms a single cell layer that surrounds the entire villus
• this layer faces the maternal blood supply

• Chronology of Morphogenesis (all days are from last menstrual period):
• day 18 (prior to implantation) – trophectoderm differentiates from inner cell mass in blastocyst
• day 21 – nidation: implantation of fetal material into uterus to form a placenta and fetus (7 days before menstruation)
• avascular trophoblast plaque rapidly grows beneath basement membrane of uterine epithelium near a spiral arteriole
• days 22-24 – spontaneous lacunae form in trophoblast plaque
• days 24-26 – establishment of maternal circulation; intervillous space is formed by invading trophoblasts which erode spiral arteries and fill lacunae
• weeks 4-4½–chorionic plate, villous stroma develop; fetal mesoderm invaginates fetal side of lacunar trophoblast plaque
• weeks 4½-5 – establishmentof fetal circulation via villous vasculogenesis
• Stroma begins to form small fetal vessels
• Pathology – if fetus dies Þ hydatidiform mole situation (hydropic abortus,edematous villi without trophoblast hyperplasia)
• called missed abortion because only detectable by ultrasound: placenta has blood supply independent of fetus
• weeks 5-8 – primary wave of implantation occurs as fetal circulation develops
• trophectoderm has formed intervillous space but has not attached to the uterus
• cytotrophoblast shell gives off Intermediate trophoblast and invades decidualized endometrium and fills arterial lumen
• Pathology – failure of implantation Þ spontaneous abortion:
• Threatened Abortion = mother is bleeding
• Incomplete Abortion = part of placenta has passed out but some remains
• Complete abortion = all of tissue passes
• Placenta Accreta = no decidualized endometrium Þ placenta grows through uterine wall
• if grows all the way through: peraccreta
• weeks 8-18 (2^nd trimester) – secondary wave of implantation is necessary to Ý circulation due to rapid growth
• trophoblast invades even deeper into the myometrium
• endovascular trophoblast invades and replaces smooth muscle wall of myometrial radial arteries
• dilates the arteries and prevents them from spasming Þ increased blood flow to intervillus space
• Pathology – defective 2^o implantation results in loss of fetus: Preclampsia (HTN disorder of pregnancy, often 1st)
• weeks 12-18 – formation of membranes – initially villi surround entire placenta Þ polarization of villi location
• only the discoid area where the umbilical cord attaches retain villi as the remainder atrophy Þ membranes
• consequently the amnion and amniotic fluid are one within a few cells of the uterine wall and endocervical canal
• Pathology–spatially inappropriate atrophy: trophoblast finds only scar or tumor when searching for best blood supply
• can result in multi parti-placenta or umbilical cord separated from the main placenta
• this results in fetal vessels in the membranes which can rupture with the membranes at time of labor
• Vesa previa = Vessels overlying the cervix; Can lead to fetal death
• Placenta previa = over lies the cervix; requires C-section
• weeks 22-30 – terminal villogenisis: formation of capillary layer of villous where all the gas exchange takes place
• necessary due to significantly increased demand of the fetus for nutrients and exchange
• Pathology–overdevelopment occurs in maternal diabetes mellitus due to large fetal size requiring Ý exchange
• Terminal villogenisis may not be able to keep up with fetal growth Þ intrauterine fetal death
• Pre-eclampsiaÞ inadequate O₂ in inter-villous space to induce terminal villi; IUGR:intrauterine growth retardation

• Basal Plate
• Abrutio Placenta – placenta separates from uterus prematurely in the 3^rd trimester
• maternal blood lifts placenta from uterus Þ premature delivery, no blood supply to intervillous space, major maternal hemorrhage
• Fetal vessels
• Meconium release – umbilical cord is occluded collapsing the umbilical vein cutting of maternal blood
• baby shunts blood to vital organs and away from gut Þ reflex peristalsis of gut causing release of green fetal stool
• only a risk factor when occurs for a long period of time. Normally not a problem (10% of all births)
• Membranes
• Acute Chorioamnionitis – intrauterine infection usually via cervix into the amniotic fluid or PID (pelvic inflammatory disease), bladder infection, maternal sepsis etc.
• causes inflammatory response; often leads to rapid delivery; response is acute so a neutraphil mediated disease
• both mother and baby respond; always directed toward the amniotic fluid, so on the chorionic plate side
• Intervillous space
• Increased syncytiotrophoblast knots – chronic uteroplacental underperfusion