自身免疫性睾丸炎中miR-155调控睾丸巨噬细胞极化导致生精损伤的研究

男性不育问题日趋严重，其中睾丸免疫异常是重要的致病因素。睾丸是免疫豁免器官，但自身免疫性睾丸炎会导致精原细胞受到免疫攻击而导致不育，具体机制不明。近年来microRNA参与免疫调控受到重视，前期研究发现，在实验性自身免疫性睾丸炎（EAO）小鼠模型中，睾丸巨噬细胞极化改变，并通过高通量测序筛选出miR-155高表达，而miR-155是重要的免疫调控miRNA。因此我们提出假设：自身免疫性睾丸炎中miR-155参与调控睾丸巨噬细胞极化，引起精原细胞功能受损而导致男性免疫性不育，推测其可作为无创检测标记物。为此，我们拟在EAO小鼠中，探索miR-155调控睾丸巨噬细胞NFκB和STAT6极化通路的机制，并在体外3D共培养体系中研究巨噬和精原细胞互作，最后探索人精浆中游离miR-155作为无创标记物的应用。本项目的完成将了解表观遗传调控免疫耐受的机制，并探索其作为免疫性男性不育的疾病靶点和标记物。

The problem of male infertility is becoming more and more serious, and abnormal testicular immunity is an important cause of the male infertility. Testis is an immune privilege organ, and the spermatogonial cells are attacked in autoimmune orchitis, However, the mechanism is unknown. In recent years, microRNAs have been paid more attention to immune regulation. Previous studies have found that testicular macrophage polarization changes in experimental autoimmune orchitis(EAO) mouse models. We found the expression of miR-155 is up-regulated by high-through sequencing and miR-155 is an important immuno-regulatory miRNA. Therefore, we hypothesized that miR-155 was involved in the regulation of testicular macrophage polarization in autoimmune orchitis, causing impaired spermatocyte function and leading to male immunological infertility, which is presumed to be a non-invasive detection marker. To this end, we intend to explore the mechanism which miR-155 regulates the polarized pathways of NFκB and STAT6 in testicular macrophages in EAO mice, and study the interaction between macrophages and spermatogonia in an in vitro 3D co-culture system. The use of cell-free miR-155 in seminal plasma as a non-invasive marker. The completion of this project will understand the mechanisms of epigenetic regulation of immune tolerance and explore its role as a biomarker for immune male infertility.