Myostatin Is Localized in Extravillous Trophoblast and Up-Regulates Migration

Abstract

Context: 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.Objective: 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.Results: 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 Ͻ .0001) and migration (HTR-8/SVneo and primary isolated EVT; P Ͻ .05), with proliferation being dose dependent and migration being dose independent. Conclusions: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. (J Clin Endocrinol Metab 99: E2288 -E2297, 2014)

Decreasing maternal myostatin programs adult offspring bone strength in a mouse model of osteogenesis imperfecta

“…The effect of myostatin on placental glucose transport is mixed, with decreased glucose transport in a choriocarcinoma cell line (27) and increased transport in human placental explants (28). Myostatin also promotes extravillous trophoblast migration in vitro, which may alter placental development in vivo (29). Uterine knockout of myostatin receptor ALK4 profoundly alters placental organization (30), as does knockout of ALK5, which additionally disrupts implantation, spiral artery remodeling, and uterine natural killer cell localization (31).…”

Oocyte–somatic cell interactions in the human ovary—novel role of bone morphogenetic proteins and growth differentiation factors

“…In the last few years, there has been a growing interest in the investigation of GDF8’s functional roles outside of the musculoskeletal systems. Notably, the expression and potential functions of GDF8 have recently been investigated in several reproductive organs, including the uterus and placenta (Islam et al ., 2014; Peiris et al ., 2014). Furthermore, data from clinical samples have highlighted the possible involvement of GDF8 in the pathogenesis of certain reproductive disorders, such as uterine myoma, pre-eclampsia and PCOS (Chen et al ., 2012; Guo et al ., 2012; Islam et al ., 2014).…”

The Effect of Glucose on the Release and Bioactivity of Exosomes From First Trimester Trophoblast Cells

“…The hypothesis to be tested is that exosomal signaling by placental cells (defined as the number of exosomes released per unit of time and their bioactivity) is responsive to extracellular glucose concentrations. The hypothesis was tested across a range of oxygen tensions that trophoblast cells are exposed to during placentation (ie,1%-8% oxygen) using a wellcharacterized in vitro primary human cell culture model (first trimester trophoblast cells) (14,20,21).…”