Abstract
The authors test the hypothesis that endothelin-1 (ET-1) modulates apoptosis in human term trophoblasts. Primary cultures of cytotrophoblasts from term human placentas (n = 5) were cultured for 16 hours total or 24 hours prior to harvest at 72 hours in atmospheres of < 1%, 8%, and 20% oxygen, in the presence of 10% serum, ET-1 (1-100 pmol/mL), both, or neither. The apoptotic cleavage products of poly-ADP-ribose polymerase and cytokeratin 18 filaments were quantified by Western analysis and immunocytochemistry. The expression of BAD, pBAD-serine112, p53, and 2 isoforms of MDM2 were quantified by immunoblotting, and endothelin A and B receptors were analyzed by immunocytochemistry. Compared to vehicle control, increasing concentrations of ET-1 reduce by 3- to 6-fold the level of apoptosis in cytotrophoblasts exposed to serum-free conditions at 20% oxygen. Similarly, syncytiotrophoblast cultures grown for 24 hours without serum in 100 pmol/mL ET-1 show a 3-fold lower level of apoptosis compared with vehicle control. ET-1 significantly reduces apoptosis in cultures exposed to 20% oxygen but not in cultures exposed to 8% or 1% oxygen. The effect of ET-1 on apoptosis in 20% oxygen is accompanied by reduced p53 expression and is correlated with enhanced expression of endothelin B receptor, compared to cultures in 8% or 1% oxygen. ET-1 reduces apoptosis in cultured human trophoblasts, and this finding suggests a role for ET-1 in protecting trophoblasts against injury.
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This work was supported by NIH HD 29190 (D.M.N.), NIH HD 45675 (Y.S.), and grants 8775 (M.C.) and 10053 (G.D.) from the Jubilee Fund, Austrian National Bank, Vienna.
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Cervar-Zivkovic, M., Hu, C., Barton, A. et al. Endothelin-1 Attenuates Apoptosis in Cultured Trophoblasts From Term Human Placentas. Reprod. Sci. 14, 430–439 (2007). https://doi.org/10.1177/1933719107305801
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DOI: https://doi.org/10.1177/1933719107305801