缺氧性精子生成减少（Hypoxic spermatogenesis reduction, HSR）是以曲精小管结构破坏、生精上皮脱落、精子密度降低为特征的综合病症，是严重危害人类生殖健康的疾病之一。对其研究时我们发现HSR病人精液中，VHA（囊泡氢离子—腺苷三磷酸酶）表达较正常对照组失代偿性降低且与疾病严重程度密切关联，表明VHA在缺氧性精子生成减少发病中起重要作用；缺氧诱导小鼠缺氧性精子生成减少模型中亦证实阻断VHA能加重小鼠曲精小管病损，致使更高曲精小管损伤程度及DR5（死亡受体5）表达；芯片结果提示缺氧诱导VHA KO小鼠24小时后，曲精小管JNK信号途径活化程度较诱导后WT小鼠高近10倍，表明保护性因子VHA能通过抑制性活化JNK信号途径，抑制DR5表达，进而减轻缺氧性精子生成减少疾病程度。本研究基于HSR病理变化作为研究基础，有望找出HSR的发病机制、对HSR临床治疗提供新思路。

Hypoxic spermatogenesis reduction is a serious disease harm to people’s health and it is a syndrome characterized associated with the destruction of seminiferous tubule, loss of seminiferous epithelium and decreased semen density. In our previous study, we proved the expression of VHA (Vesicle H+-ATPase) was significantly decreased in HSR patients compared with healthy control. In addition, we found that VHA-/- mice displayed augmented damage of seminiferous tubule and significant expression of DR5 compared with wildtype littermates after treated by hypoxia. Furthermore, Chip and western blot showed higher activation of JNK signal pathway in VHA-/- mice compared to the control after hypoxia stimulated 24h, suggested VHA could inhibit the activation of downstream JNK signal pathway which regulate the expression of DR5, reduced the degree of HSR. This study was based the pathological changes of HSR and the recent investigation of VHA in a mouse HSR model has provided insights into mechanisms underlying the disease pathogenesis and resulted in some novel treatment strategies.