Myostatin is localized in extravillous trophoblast and up-regulates migration

Myostatin is a highly conserved secretory protein that negatively regulates muscle development by affecting both proliferation and differentiation of muscle cells. In human placentae the expression of myostatin is negatively correlated with gestational age, and in placental explants, myostatin acts to facilitate glucose uptake. Myostatin expression is known to be higher in the placentae of pregnancies complicated by preeclampsia. Proper placental development is crucial for a healthy and successful pregnancy. Alterations to the function of the placental cells after treatment with myostatin have not previously been published.This study investigated the localization of myostatin in extravillous trophoblast (EVT) of human placentae. Furthermore, the effect of myostatin treatment on the proliferative and migrative capabilities of these placental cells was investigated.Myostatin is localized in EVT, as identified by the immunohistochemistry of third-trimester placentae and immunocytochemistry of first-trimester EVT isolations positively staining for myostatin and human leukocyte antigen-G. Treatment of an EVT cell line (HTR-8/SVneo) and primary isolated EVT with varied concentrations of myostatin resulted in a significant increase in the proliferation (HTR-8/SVneo; P.0001) and migration (HTR-8/SVneo and primary isolated EVT; P.05), with proliferation being dose dependent and migration being dose independent.Myostatin localization was positively identified in EVT. Myostatin positively affected proliferation (HTR-8/SVneo) and migration of EVT (HTR-8/SVneo and primary isolated EVT). For the first time, the effect of myostatin treatment on placental cells is described. The results provide a base from which further in vitro investigations on myostatin's ability to modulate placental cell function can be made.