Advances in Understanding the Molecular Mechanisms of Activin A-Regulated Biological Characteristics in Human Trophoblasts and Its Dysregulation in Placenta-Derived Pregnancy Disorders

During the establishment of human pregnancy, embryonic trophoblast cells are in direct contact with the endometrium, closely mediate the maternal-fetus dialogue, regulate embryo implantation and gradually form the placenta, which is responsible for maintaining material exchange and nutrient supply throughout pregnancy. A subset of trophoblast cells invade and migrate into the maternal decidual tissue, remodeling the uterine spiral arteries, which is essential for placental formation and blood supply. Abnormalities in biological characteristics such as trophoblast invasion, migration, proliferation, apoptosis, and acquisition of endothelial-like phenotype are important causative factors in various placenta-derived pregnancy disorders, including embryo implantation failure, miscarriage, gestational trophoblastic diseases, PE (preeclampsia), and FGR (fetal growth restriction). Activin A, a secreted protein belonging to the TGF-β superfamily, is abundantly present in the maternal circulation and at the maternal-fetal interface during pregnancy, which plays key roles in regulating the biological characteristics of trophoblasts and the establishment and maintenance of pregnancy. This paper reviews the molecular mechanisms through which activin A regulates the biological characteristics of human trophoblasts and its dysregulation in placenta-derived pregnancy disorders.