Villous Development
-12-18 days GA --> trophoblastic trabeculae form the Primary Villi, projecting into maternal blood, then after 2 days they're invade by embryonic CT--> Secondary Villi
-18-20 days GA --> fetal capillaries appear --> Tertiary Villi
-initially mesencymal villi = first struture for maternal-fetal exchange
-20-42 days GA --> mesench villi start vasculogenesis to make new capillaries fr the mesenchymal precursor cells
-Mesenchymal villi- can differentiate into specialized villi
-Week 23 GA- mature intermediate villi differentiate to make terminal villi which have many capillaries, for exchange...; some mesenchymal & immature intermediate remain in the tree, as a reserve for growth...
-... genes involved...
Invasion & Implantation
-Trophoblasts are teh 1st to differentiate in an embryo - adhere to uterus, initiate implantation
-retain stem cell population of villous cytotrophoblasts throughout pregnancy
-can --> either syncytiotrophoblast lineage, or invasive cytotrophoblast lineage...
-Syncytiotrophoblasts of chorionic villi - repsonsible for placental nutrient/gass exchange, and for placental hormone/growth factor synth.
-Fetal arteries and vein develop within the chorionic villi
-Invasive Cytotrophoblasts- start to prolif into cell columns early, from which extravillous throphoblasts emanate to --> interstitial/endovascular invasive trophoblasts, the interstitial ones going to to invade the uterus and anchor placenta to uterus, the endovascular ones go to the maternal uterine spiral arteries, where they convert the spiral arteries by replacing the endothelial cell lining of the vessel. --> form vessels w low resistance, high capacitance to meet need of increased blood Q..., occurs by end of 1st Trimester
-failure of invasion appropriately can --> preeclampsia
-during the conversion of the spiral muscles, there is loss of muscle/elastic tissue around the arteries, and endothel cells are replaced by trophoblasts; w preeclampsia the invasion may be superficial, not penetrate to 1/3 the myometrial layer proximal to the decidua, & the spiral artery mean diameter is low, so narrow spiral arteries--> poor placental Q
Extracellular Matrix Degredation
-ECM digestion induced by trophoblasts to allow for invasion
Trophoblast Adhesion Molecule Expression
-adhesion molecules/integrins important for migration
Placental Vasculogenesis & Angiogenesis
-decreased vasc dvp/incr vasc resistance seen w early embryo loss
-extensive incr in uterine/umbilical Q seen w the establishment of fetal circulation
Natural Killer Cells
-certain mixes of fetal and maternal genotypes incr risk of fetal loss, while certain maternal haplotypes may be protective for preeclambsia
-NK cells needed for angiogenesis and artery remodeling at fetal-maternal interface - they interact w trophoblasts, GF sec'n, cytokines, etc to enahnce spiral artery widening and troph invasion
-overinhibition of NK cells --> incr preeclampsia, decr secn of certain cytokines/growth facotors...
-NK cells help trophoblasts invade by signaling them/directing them w chemokines...
-maternal and fetal NK cells interact/cross talk...
Maternal Immune Tolerance to the Fetus
-trophoblasts closely assoc w maternal NK cells, so important that the NK cells don't kill them
-cytokine production/cross talk by WBCs and non-WBCs modulate local cytokine profile to control extravilli trophoblast (EVT) invasion
-EVG expresses 2 non-classical MHC proteins HLA-E and HLA-G, along w the classical HLA C --> prevents rejection of semi-allogenic fetus by mom as most cytotixic T cells (mom's) are directed against HLA A and HLA B which are not on the EVT cells
......