滋养层细胞生理性增殖、迁移和对蜕膜的适度侵蚀，是确保胚胎着床和早期发育的关键。此过程异常将导致死胎、妊娠高血压综合征、早产和滋养层细胞疾病等。申请人和课题组近年在国家杰出青年科学基金等资助下研究发现，stathmin-1(STMN1)通过与基质金属蛋白酶、钙连蛋白等分子以及蜕膜巨噬细胞相互作用，调控滋养层细胞增殖和迁移。此外发现母-胎界面存在滤泡辅助性T(Tfh)细胞，并对其表型和功能进行了初步研究。详细功能和调控机制尚未阐明。本项目拟在此基础上深入研究，采用RNA干扰、特异性增强或抑制技术、磁珠亲和细胞分选和Transwell细胞共培养技术等，利用临床样本、模式动物或细胞培养系统，逐步阐明STMN1等候选分子对蜕膜巨噬细胞、Tfh细胞功能的影响，解析信息转导通路上、下游关键因素相互关系，逐步阐明滋养层细胞功能及其调控机制，为提高妊娠相关疾病预防和诊治水平提供科学依据。

Trophoblast proliferation, migration and adequate invasion to decidua is critical for implantation and development of early-stage embryos. Recently, our group found that stathmin-1 (STMN1) plays a key role in modulating trophoblast proliferation and migration by interacting with matrix metalloproteinases (MMPs), caderins and decidual macrophage subsets, and found that there are plenty of T follicular helper (Tfh) cells at the feto-maternal microenvironment. The phenotype and function of these cells was preliminarily investigated. However, the detailed mechanism remains to be clarified. Herein, we aim to clarify the mechanisms by which STMN1 and other candidate molecules interact with decidual macrophage and Tfh cell subsets and transduce cell signals to modulate trophoblast functions, and clarify their relationship with pregnancy-related disorders. Specific enhancing and inhibiting techniques including RNA interfering, together with megnetic-affinity cell sorting and transwell coculture techniques will be used as major methods, while clinical samples, animal models and cell culture systems will be used as materials in our researches. The expected findings will provide evidence and surely be beneficial for improving prevention, diagnosis and treatment of pregnancy-related disorders.