缺氧经HIF1α/ GATA3/ TGFβ途径调控滋养细胞侵袭的机制以及在自然流产发生中的作用研究

妊娠早期反复流产（RSA）是产科常见并发症，胎盘绒毛外滋养细胞（Extravillous trophoblast，EVT）侵袭不足是导致RSA发生的重要原因之一，机制尚未完全阐明。本项目的前期研究发现转录因子GATA3在孕早期EVT中高表达，敲低其表达可抑制EVT细胞侵袭，GATA3表达下降可能与RSA的发生相关。本研究拟通过分子细胞生物学等技术探究GATA3响应缺氧诱导经HIF1α/ GATA3/ TGFβ途径调控滋养细胞侵袭的机制，明确GATA3在自然流产发生中的作用。并通过CUT&Tag技术进一步探究GATA3在EVT细胞中的调控靶标，明确其在滋养细胞侵袭及流产发生过程中的作用机制，为RSA的早期诊断及靶向治疗提供新的思路。

Recurrent Spontaneous Abortion (RSA) is a common complication in obstetrics. Insufficient invasion of Extravillous trophoblast (EVT) is one of the important causes of RSA, and the mechanism has not been fully elucidated. Our preliminary study found that transcription factor GATA3 was highly expressed in EVT during early pregnancy. Knocking down its expression could inhibit the invasion of EVT. The decreased expression of GATA3 may be related to the occurrence of RSA. In this study, we plan to explore the mechanism of GATA3 regulating trophoblast invasion in response to hypoxia induction via HIF1α/ GATA3 / TGFβ pathway, and to definite the regulation role of GATA3 in RSA. The regulatory target of GATA3 in EVT cells was further explored by CUT& Tag technique, and to clarify its mechanism in trophoblast cell invasion which provide a new idea for the early diagnosis and targeted therapy of RSA.