State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, 1 Beichen West Road, Chaoyang District, Beijing100101, People's Republic of China.
J Clin Endocrinol Metab. 2012 Aug;97(8):E1370-9. doi: 10.1210/jc.2011-2729. Epub 2012 Jun 8.
The pregnancy-specific disorder preeclampsia is a major cause of maternal mortality and morbidity. Activin A has been suggested as a potential biomarker of the disease, but whether it plays a role in the pathology of preeclampsia or is just a manifestation of the disease is not fully understood.
The objective of the study was to examine the roles of Activin A on placental trophoblast cells under pathological conditions of preeclampsia.
Placental and plasma productions of Activin A in healthy pregnant women and preeclamptic patients were compared by using clinical samples obtained from Peking University First Hospital during November 2005 to November 2007. The role of Activin A at pathological doses was investigated in human trophoblast cells.
Plasma and placental productions of Activin A were significantly higher in preeclamptic patients when compared with normal pregnant subjects in a Chinese Han population. Treatment of trophoblast cells with high doses of Activin A resulted in a significant increase in cell apoptosis. This effect was blocked not only by silencing Activin A's receptor activin receptor-like kinase 4 but also by knockdown of Nodal's receptor ALK7. Important to note was that Activin A could significantly increase Nodal expression in trophoblast cells, and knockdown of Nodal resulted in evident blockage on Activin A-induced trophoblast cell apoptosis.
High levels of Activin A observed in preeclamptic placenta may play a role in the pathogenesis of preeclampsia by inducing excessive apoptosis in placenta indirectly through enhancing Nodal expression.
妊娠特有疾病子痫前期是孕产妇发病率和死亡率的主要原因。激活素 A 已被认为是该疾病的一个潜在生物标志物，但它是否在子痫前期的病理中起作用，还是仅仅是该疾病的一种表现，尚不完全清楚。
本研究旨在研究激活素 A 在子痫前期病理条件下对胎盘滋养层细胞的作用。
本研究使用北京大学第一医院于 2005 年 11 月至 2007 年 11 月期间获得的临床样本，比较了健康孕妇和子痫前期患者的胎盘和血浆中激活素 A 的产生。在人滋养层细胞中研究了激活素 A 在病理剂量下的作用。
与中国汉族正常孕妇相比，子痫前期患者的血浆和胎盘激活素 A 产生明显升高。用高剂量激活素 A 处理滋养层细胞会导致细胞凋亡明显增加。这种作用不仅可以通过沉默激活素 A 的受体激活素受体样激酶 4 来阻断，也可以通过 Nodal 的受体 ALK7 的敲低来阻断。值得注意的是，激活素 A 可显著增加滋养层细胞中 Nodal 的表达，而 Nodal 的敲低可明显阻断激活素 A 诱导的滋养层细胞凋亡。
子痫前期胎盘观察到的高水平激活素 A 可能通过增强 Nodal 表达间接诱导胎盘过度凋亡，从而在子痫前期的发病机制中起作用。
