The trophoblast epithelial-to-mesenchymal transition (EMT) is a procedure related to embryo implantation, spiral artery establishment and fetal-maternal communication, which is a key event for successful pregnancy. Inadequate EMT is one of the pathological mechanisms of recurrent miscarriage (RM). Whole-exome sequencing revealed that the mutation of bromodomain PHD-finger transcription factor (BPTF) was strongly associated with RM. In the present study, the effects of BPTF on EMT and the underlying mechanism were investigated. We found that the expression of BPTF in the villi of RM patients was significantly downregulated. Gene Ontology (GO) analysis revealed that BPTF participated in cell adhesion. The knockdown of BPTF prevented EMT and attenuated trophoblast invasion in vitro. BPTF activated Slug transcription by binding directly to the promoter region of the Slug gene. Interestingly, the protein levels of both Slug and BPTF were decreased in the villous cytotrophoblasts (VCTs) of RM villi. In conclusion, BPTF participates in the regulation of trophoblast EMT by activating Slug expression, suggesting that BPTF defects are an important factor in RM pathogenesis.

中文翻译：

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溴结构域 PHD-finger 转录因子 (BPTF) 对滋养层上皮间质转化的影响

滋养层上皮间质转化（EMT）是与胚胎着床、螺旋动脉建立和母胎沟通相关的过程，是成功妊娠的关键事件。 EMT不足是复发性流产（RM）的病理机制之一。全外显子组测序显示，布罗莫结构域 PHD 指转录因子 (BPTF) 的突变与 RM 密切相关。在本研究中，研究了BPTF对EMT的影响及其潜在机制。我们发现 RM 患者绒毛中 BPTF 的表达显着下调。基因本体（GO）分析表明BPTF参与细胞粘附。 BPTF 的敲低可阻止 EMT 并减弱体外滋养层的侵袭。 BPTF 通过直接结合到 Slug 基因的启动子区域来激活 Slug 转录。有趣的是，在 RM 绒毛的绒毛细胞滋养细胞 (VCT) 中，Slug 和 BPTF 的蛋白水平均降低。总之，BPTF通过激活Slug表达参与滋养层EMT的调节，提示BPTF缺陷是RM发病机制的重要因素。