HIF-1对小鼠睾丸间质细胞合成睾酮的影响及机制探讨

睾丸组织局部缺血缺氧，是导致职业性男性不育发生的重要原因。低氧可导致雄性动物睾酮水平下降，精子畸形率增加，精液质量严重下降。前期研究表明，低氧或常氧条件下，细胞合成睾酮水平均与HIF-1蛋白水平负相关，提示HIF-1为低氧条件下导致睾酮水平下降的主要原因。基于前期研究结果，为探讨低氧条件下重要调节蛋白HIF-1对睾丸间质细胞合成睾酮的影响及机制，本课题拟开展以下研究：①通过研究低氧刺激后雄性Balb/c小鼠睾丸组织结构、血清睾酮水平的变化，评估低氧刺激对雄性Balb/c小鼠生殖系统的影响；②通过研究常氧、低氧条件下HIF-1对TM3细胞合成睾酮的影响，确定HIF-1对睾酮合成的调控作用；③探讨常氧、低氧条件下HIF-1调控睾酮合成的具体分子机制，为防治缺氧性男性不育提供基础数据。

Testicular tissue hypoxia/ischemia is an important cause of infertility. Hypoxia leads to decreased testosterone levels in male animals, increased percentage of abnormal sperm and a serious decline in semen quality. Our preliminary studies found that under both normoxic and hypoxic conditions, there was a negative correlation between HIF-1 expression and the testosterone synthesis in Leydig cells, indicating that HIF-1 might be the main reason leading to the decline of serum testosterone under hypoxic condition. This project aims to explore the effect of HIF-1 on testosterone synthesis in Leydig cells and underlying mechanisms under hypoxic conditions. Based on our preliminary findings, these following studies are to be carried out: ① Analyse changes in testicular tissue structure and serum testosterone level in male Balb/c mice under hypoxic condition to assess the impact of hypoxia on the reproductive system in male Balb/c mice; ② Study the regulatory effect of HIF-1 on TM3 cells under normoxic or hypoxic conditions to verify HIF-1 regulation of testosterone synthesis; ③ Investigate the underlying molecular mechaisms of HIF-1 regulation of testosterone synthesis under normoxic and hypoxic conditions to provide basic data for the prevention and treatment of hypoxic male sterility.