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It is now well accepted that the placenta develops under low-oxygen tension during the first trimester of pregnancy. However, it is currently recognized that pregnancy-related diseases such as preeclampsia and fetal growth restriction are linked to a persistent oxidative stress in the placenta during the second and the third trimesters. Using siRNA in primary villous cytotrophoblasts (n=4 placentas), we assessed the role of EPAS1 in the syncytialization process. Reducing EPAS1 expression increased their differentiation into syncytiotrophoblasts under low oxygen tension, which was illustrated by an enhanced fusion index (20.18% vs. 30.95%, p<0.05) and a higher βHCG and PGF secretion after transfection (2.82 and 3.19 times more respectively, p<0.01). To confirm these results, we created an oxygen-resistant mutant EPAS1. Its surexpression in JEG3 and BeWO cell lines represses the expression of βHCG and PGF while it increased the sFLT1 expression. In conclusion, these experiments highlight the main role of EPAS1 in the formation of the syncytium and suggest that an abnormal activity of this factor could partially explain the physiopathology of the main obstetrical syndromes.
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Colson, A., Depoix, C., Hubinont, C., Sonveaux, P., Debiève, F., & et al. (2019). Oxygen-resistant Hypoxia-Inducible Factor-2a (EPAS1) Mutant Inhibits Forskolin-induced Differentiation of Choriocarcinoma Cell Line BeWo. CTR Annual Conference, Cambridge. https://hdl.handle.net/2078.5/247762