High Levels of Activin A Detected in Preeclamptic Placenta Induce Trophoblast Cell Apoptosis by Promoting Nodal Signaling

Context: 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. Objective: The objective of the study was to examine the roles of ActivinAon placental trophoblast cells under pathological conditions of preeclampsia. Design: Placental and plasma productions of ActivinAin 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. Results: 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. Conclusion: 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. (J Clin Endocrinol Metab 97: E1370-E1379, 2012)