激活素A调控人类滋养细胞生物学特性的分子机制及其与胎盘源性妊娠疾病关系的研究进展

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

在人类妊娠建立过程中,胚胎滋养外胚层细胞与子宫内膜直接接触,严密介导母胎对话,调控胚胎着床、植入宫腔,并逐渐形成维持妊娠期间物质交换、营养供应的胎盘组织。起源于滋养外胚层的一部分滋养细胞(trophoblast)侵袭、迁移进入母体蜕膜组织,重塑子宫螺旋小动脉,对于胎盘形成和母胎血液循环建立至关重要。滋养细胞侵袭、迁移、增殖、凋亡、内皮特性获得等生物学特性异常是胚胎种植失败、自然流产、妊娠滋养细胞疾病、子痫前期、胎儿生长受限等胎盘源性妊娠疾病的重要因素。激活素A(activin A)作为转化生长因子β(transforming growth factor-β,TGF-β)超家族中的一种分泌型蛋白,在妊娠期间母体循环及母胎界面表达丰富,在调控滋养细胞生物学特性以及妊娠的建立和维持中起重要作用。该文主要围绕激活素A调控人类滋养细胞生物学特性的分子机制及其在胎盘源性妊娠疾病中表达改变的研究进展进行综述。

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-βsuperfamily,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.