lncRNA SNHG5调控miR-20a在稀土Nd2O3致雄性生精细胞损害及不育的分子机制研究

男性不育症已成为影响人类健康和发展的全球性医学问题，稀土氧化钕作为高精尖产业必不可少的原材料应用日益广泛，可导致稀土尘肺发生。课题组率先发现稀土尘肺患者血浆中差异表达的lncRNA SNHG5在睾丸中分布表达及氧化钕可致雄性小鼠精子数量减少，睾丸组织出现病理性变化。氧化钕与男性生殖系统损害及不育发生、发展的关系，迄今国内外尚无报道。我们推测氧化钕暴露过程中，通过上调SNHG5的表达抑制miR-20a，使其靶蛋白p38 MAPK水平升高而激活p38 MAPK信号通路引起生精细胞凋亡。为证实这一假说，从人群-动物-细胞三个层次，采用qRT-PCR、W-B、基因敲除/过表达等技术，观察SNHG5通过调控miR-20a在Nd2O3致雄性生精细胞损害及不育中作用，探讨SNHG5和miR-20a作为生精细胞损害及不育的早期分子标志，为寻找氧化钕致生殖系统损害作用的有效治疗药物提供新思路。

Male infertility has become a global medical and sociological issue that affects human health and development. The rare earth neodymium oxide (Nd2O3) is widely used as an essential raw material for high-tech industries, which can lead to the occurrence of rare earth pneumoconiosis. Our research group was the first to find that the differentially expressed lncRNA SNHG5 in the plasma of rare earth pneumoconiosis patients was distributed and expressed in the testes, and Nd2O3 could lead to a decrease in sperm counts in male mice and pathological changes in testicular tissues. The relationship between Nd2O3 and the occurrence and development of male reproductive system damage and infertility has not been reported so far at home and abroad. We speculate that during Nd2O3 exposure, miR-20a is adsorbed by up-regulating the expression of lncRNA SNHG5 to increase the level of target protein p38 MAPK and activate the p38 MAPK signaling pathway to cause spermatogenic cell apoptosis. To confirm this hypothesis, we will observe the mechanism of SNHG5 inducing spermatogenic cell damage and infertility by regulating miR-20a from the population-animal-cell level and the experimental techniques include q-RT-PCR, Weston-Blot, Double luciferase reporter gene experiment, gene knockout / overexpression, etc. This topic will discuss SNHG5 and miR-20a as early molecular markers of spermatogenic cell damage and infertility, and to provide a new perspective of searching for effective therapeutic drugs for the damage of reproductive system caused by Nd2O3.