Growth differentiation factor myostatin regulates epithelial‐mesenchymal transition genes and enhances invasion by increasing serine protease inhibitors E1 and E2 in human trophoblast cells

Placental insufficiency disorders, including preeclampsia and intrauterine growth restriction, are major obstetric complications that can have devastating effects on both the mother and the fetus. These syndromes have underlying poor placental trophoblast cell invasion into uterine tissues. Placental invasion is controlled by many hormones and growth factors. Myostatin (MSTN) is a transforming growth factor‐β superfamily member recognized for its important role in muscle growth control. MSTN has also been shown to be secreted and functioning in the placenta, and its serum and/or placental levels were found to be upregulated in preeclampsia and intrauterine growth restriction. Considering that the mechanistic role of MSTN in placentation remains poorly understood, we hypothesized that MSTN uses ALK4/5‐SMAD2/3/4 signaling to increase human trophoblast invasion through a group of epithelial–mesenchymal transition genes including SERPINE2, PAI‐1, and SOX4. mRNA sequencing of control and MSTN‐treated primary human trophoblast cells (n = 5) yielded a total of 610 differentially expressed genes (false discovery rate