Molecular Mechanisms of Trophoblast Dysfunction Mediated by Imbalance between STOX1 Isoforms

STOX1 is a transcription factor involved in preeclampsia and Alzheimer disease. We show that the knock-down of the gene induces rather mild effect on gene expression in trophoblast cell lines (BeWo). We identified binding sites of STOX1 shared by the two major isoforms, STOX1A and STOX1B. Profiling gene expression of cells overexpressing either STOX1A or STOX1B, we identified genes downregulated by both isoforms, with a STOX1 binding site in their promoters. Among those, STOX1-induced Annexin A1 downregulation led to abolished membrane repair in BeWo cells. By contrast, overexpression of STOX1A or B has opposite effects on trophoblast fusion (acceleration and inhibition, respectively) accompanied by syncytin genes deregulation. Also, STOX1A overexpression led to abnormal regulation of oxidative and nitrosative stress. In sum, our work shows that STOX1 isoform imbalance is a cause of gene expression deregulation in the trophoblast, possibly leading to placental dysfunction and preeclampsia. [Display omitted] •STOX1, involved in preeclampsia, recognizes specific DNA sequences•Downregulation of STOX1 isoforms has limited effect on trophoblast gene expression•Overexpression of STOX1A and B leads to downregulation of some genes•Overexpression of STOX1A or STOX1B leads to opposite effects on other genes Reproductive Medicine; Molecular Biology; Developmental Biology