Mammalian Ste20‐like Protein Kinase 3 (Mst3) Plays an Important Role in Spontaneous Delivery

Abstract

It has been shown that prior term labor a substantial population of trophoblasts of human fetal membrane underwent apoptosis. The apoptosis was thought to be induced by oxidative stress with the evidence that women in active labor exhibited high level serum hydroperoxides. Thus, oxidative stress is postulated to be involved in initiating the labor process. To understand the molecular mechanism underlying the oxidative stress-induced trophoblast apoptosis we checked the signs of oxidative stress, DNA fragmentation, caspase 3 activation and Mst3 expression in the human full term and selective cesarean placenta and 6~8 weeks endometrium spacemen by Immunohistochemistry. Mst3 is a human Ste20-like protein kinase that may play a role in apoptosis in response to apoptotic signals. Interestingly, compared with cytotrophoblasts in the first-trimester of pregnancy and selective cesarean placenta, we found that the cytotrophoblasts underwent an extensive apoptosis in a full term placenta. Furthermore, the cytotrophoblasts at full term placenta contained high level Mst3 and nitrotyrosine, a marker of oxidative stress, which were undetectable in trophoblasts of first-trimester and of selective cesarean placenta. The H2O2-induced apoptosis and Mst3 overexpression were also observed in a human cytotrophoblast cell line 3A-sub-E through in vitro studies. These results suggest that the apoptosis of cytotrophoblasts in active labor may be induced by oxidative stress in the Mst3-dependdent manner. (The work was financially supported by National Science Council, ROC (Taiwan) under Contract No. NSC-94-2311-B-009-003.)