The familial forms of early-onset pre-eclampsia and related syndromes (Hemolysis, Elevated Liver enzymes, Low Platelets) (HELLP) associated with intrauterine growth restriction (IUGR) involve fetal genes expressed in the placenta controlling key components in signaling cascades essential for extravillus trophoblast (EVT) function. The key components run in parallel or interact via cross-talk but converge in a common pathway: trophoblast invasion. In normal pregnancy, the mechanism of trophoblast invasion into the maternal placental bed establishes an essential connection between the maternal and fetal circulations. Failure of this local, early process by (epi)genetic defects leads to aberrant trophoblast differentiation with incomplete maternal vessel wall adaptation in the placental bed. This local defect is followed by compensatory mechanisms of the hypoxic placenta. Placental changes in the release of PlGF, sEng and sFlt trigger maternal TGFß-dependent NOS-mediated vasodilation. Finally, months after the initial event, maternal endothelial cell damage with systemic symptoms (hypertension, proteinuria, convulsion, elevated liver enzymes, low platelets) results. The (epi)genetic control of human trophoblast invasion is central in this sequence of events. This speciality section of Frontiers in Genetics provides a snapshot of the state of the art of the various genetic and epigenetic aspects of this important biological process.
The familial forms of early-onset pre-eclampsia and related syndromes (Hemolysis, Elevated Liver enzymes, Low Platelets) (HELLP) associated with intrauterine growth restriction (IUGR) involve fetal genes expressed in the placenta controlling key components in signaling cascades essential for extravillus trophoblast (EVT) function. The key components run in parallel or interact via cross-talk but converge in a common pathway: trophoblast invasion. In normal pregnancy, the mechanism of trophoblast invasion into the maternal placental bed establishes an essential connection between the maternal and fetal circulations. Failure of this local, early process by (epi)genetic defects leads to aberrant trophoblast differentiation with incomplete maternal vessel wall adaptation in the placental bed. This local defect is followed by compensatory mechanisms of the hypoxic placenta. Placental changes in the release of PlGF, sEng and sFlt trigger maternal TGFß-dependent NOS-mediated vasodilation. Finally, months after the initial event, maternal endothelial cell damage with systemic symptoms (hypertension, proteinuria, convulsion, elevated liver enzymes, low platelets) results. The (epi)genetic control of human trophoblast invasion is central in this sequence of events. This speciality section of Frontiers in Genetics provides a snapshot of the state of the art of the various genetic and epigenetic aspects of this important biological process.
