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 Activin A on placental trophoblast cells under pathological conditions of preeclampsia. DESIGN: 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. 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.
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 Activin A on placental trophoblast cells under pathological conditions of preeclampsia. DESIGN: 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. 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.
Authors: Sarah C Moody; Penny A F Whiley; Patrick S Western; Kate L Loveland Journal: Front Endocrinol (Lausanne) Date: 2022-05-31 Impact factor: 6.055
Authors: Ina A Stelzer; Mohammad S Ghaemi; Xiaoyuan Han; Kazuo Ando; Julien J Hédou; Dorien Feyaerts; Laura S Peterson; Kristen K Rumer; Eileen S Tsai; Edward A Ganio; Dyani K Gaudillière; Amy S Tsai; Benjamin Choisy; Lea P Gaigne; Franck Verdonk; Danielle Jacobsen; Sonia Gavasso; Gavin M Traber; Mathew Ellenberger; Natalie Stanley; Martin Becker; Anthony Culos; Ramin Fallahzadeh; Ronald J Wong; Gary L Darmstadt; Maurice L Druzin; Virginia D Winn; Ronald S Gibbs; Xuefeng B Ling; Karl Sylvester; Brendan Carvalho; Michael P Snyder; Gary M Shaw; David K Stevenson; Kévin Contrepois; Martin S Angst; Nima Aghaeepour; Brice Gaudillière Journal: Sci Transl Med Date: 2021-05-05 Impact factor: 17.956
Authors: Hari Krishna Thulluru; Craig Park; Daniel Dufort; Gunilla Kleiverda; Cees Oudejans; Marie van Dijk Journal: Front Genet Date: 2013-08-27 Impact factor: 4.599