Estradiol promotes trophoblasts syncytization by upregulating ESR2/SP1 transcription factor-mediated poFUT2 expression.

The multinucleated syncytiotrophoblast (STB) at the maternal-fetal interface is formed through the continuous fusion of mononucleated cytotrophoblasts (CTBs). Estradiol and protein glycosylation are known to participate in trophoblast syncytialization. O-fucosyltransferase 2 (poFUT2), which catalyzes protein O-fucosylation, has been implicated in placental development. However, the exact role of poFUT2 in trophoblast syncytialization remains unclear. The aim of the present study is to investigate the function of the estradiol-poFUT2 axis in trophoblast syncytialization. Here, by applying immunohistochemistry, we found that poFUT2 expression was decreased in syncytiotrophoblast of placental tissues from preeclampsia patients. Employing a cell-model to induce trophoblast syncytialization in vitro, we demonstrated that poFUT2 promotes trophoblast cell fusion. Mechanistically, during pregnancy, elevated estradiol upregulated the expression of poFUT2 and enhanced syncytium formation. Chromatin immunoprecipitation and co-immunoprecipitation assays indicated that the regulation depends on the participation of SP1 in the estrogen receptor 2 (ESR2)-mediated regulation of the poFUT2 gene. Conclusively, our findings demonstrated that estradiol upregulated poFUT2 expression via the ESR2/SP1 complex, increasing trophoblast cell differentiation and fusion.