High levels of activin A detected in preeclamptic placenta induce trophoblast cell apoptosis by promoting nodal signaling.
BACKGROUND
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.


METHODS
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.


CONCLUSIONS
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.
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.
Ling
L
Yu
Dong
D
Li
Qin-Ping
QP
Liao
Hui-Xia
HX
Yang
Bin
B
Cao
Guodong
G
Fu
Gang
G
Ye
Yang
Y
Bai
Hao
H
Wang
Nana
N
Cui
Ming
M
Liu
Yu-Xia
YX
Li
Jun
J
Li
Chun
C
Peng
Yan-Ling
YL
Wang
D030201:Activin Receptors, Type I / Q000502:physiology; D028341:Activins / Q000032:analysis / Q000502:physiology*; D000328:Adult; D000595:Amino Acid Sequence; D017209:Apoptosis; D016022:Case-Control Studies; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D020782:Matrix Metalloproteinases / Q000502:physiology; D008969:Molecular Sequence Data; D010920:Placenta / Q000737:chemistry*; D011225:Pre-Eclampsia / Q000209:etiology / Q000378:metabolism*; D011247:Pregnancy; D011446:Prospective Studies; D015398:Signal Transduction / Q000502:physiology*; D014327:Trophoblasts / Q000473:pathology*
C422405:activin A; D028341:Activins; C498932:ACVR1B protein, human; C424205:ACVR1C protein, human; D030201:Activin Receptors, Type I; D020782:Matrix Metalloproteinases