精子数量是影响男性生殖能力的重要因素。我们前期流行病学调查发现慢性心理应激可能导致精子数量下降，实验分析发现糖皮质激素(GC)参与了早期生精细胞损伤，机制筛选发现与糖皮质激素受体(GR)表达调控相关的miR-204变化最为显著，因此推测在慢性应激诱导的精子损伤过程中，miR-204可能通过调控GR受体及其下游关键分子GILZ诱发了早期生精细胞凋亡。因此，本项目拟建立CUMS动物模型及小鼠精母细胞Dex染毒模型，系统分析GC以及GC-GR-GILZ通路在慢性应激导致早期生精细胞凋亡中的作用及机制；初步探索miR-204对GC-GR-GILZ通路的调控分子机理。本研究对于深入了解慢性应激致男性生殖损伤的机制和维护男性生殖健康提供新的理论依据。

Sperm number is the key index of male fertility. Our previous epidemiological studies in healthy men suggested that the chronic psychological stress was associated with decreased sperm number in the population, but the underlying mechanism remains unknown. Our data suggest that glucocorticoid (GC) can induce the apoptosis of early spermatogenic cells and significantly decreased the expression of miR-204 which was related to regulation of the glucocorticoid receptor (GR) expression. Thus, we hypothesized that miR-204 may involved in the apoptosis of early spermatogenic cells induced by chronic psychological stress through the regulation of GR expression and the key down-stream protein GILZ related to cell apoptosis. In order to validate the hypothesis above, we plan to analysis the role of GC and GC-GR-GILZ pathway in the apoptosis of early spermatogenic cells induced by chronic psychological stress, and investigate the role of miR-204 in the regulaiton of GC-GR-GILZ pathway based upon the CUMS animal model and GC-2 cells with dexamethasone administration. This study will help us to understand the mechanism spermatozoa damage induce by chronic psychological stress and to keep the male fertility in population.