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

Abstract

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: Ling Yu, Dong Li, Qin-Ping Liao, Hui-Xia Yang, Bin Cao, Guodong Fu, Gang Ye, Yang Bai, Hao Wang, Nana Cui, Ming Liu, Yu-Xia Li, Jun Li, Chun Peng, Yan-Ling Wang
• Journal: The Journal of clinical endocrinology and metabolism (J Clin Endocrinol Metab) Vol. 97 Issue 8 Pg. E1370-9 (Aug 2012) ISSN: 1945-7197 [Electronic] United States
• PMID: 22685232 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• activin A
• Activins
• ACVR1B protein, human
• ACVR1C protein, human
• Activin Receptors, Type I
• Matrix Metalloproteinases

Topics

• Activin Receptors, Type I (physiology)
• Activins (analysis, physiology)
• Adult
• Amino Acid Sequence
• Apoptosis
• Case-Control Studies
• Cells, Cultured
• Female
• Humans
• Matrix Metalloproteinases (physiology)
• Molecular Sequence Data
• Placenta (chemistry)
• Pre-Eclampsia (etiology, metabolism)
• Pregnancy
• Prospective Studies
• Signal Transduction (physiology)
• Trophoblasts (pathology)