睾丸Leydig细胞老化，睾酮合成能力降低，容易导致性欲减退、骨质疏松和糖尿病，最终降低男性整体生活质量。我们假设：Leydig细胞老化相关的生物学变化会增加老化Leydig细胞对急性氧化应激的易感性。因此，衰老是环境因素对睾丸Leydig细胞影响的高危因素。本项目探讨衰老在老年Leydig细胞对急性氧化应激易感性中所起的作用。以大鼠和转基因小鼠（2种γ-谷氨酰半胱氨酸连接酶和Nrf2敲除）的年轻和老年Leydig细胞，用环境污染物包括叔丁基过氧化氢和邻苯二甲酸酯类实验诱发细胞内氧化还原环境的改变，以及在体实验，探索Leydig细胞急性应激易感性之间的因果关系和MAPK信号传导作用，确定Nrf2/Keap1信号系统在调节老化Leydig氧化还原环境改变中的作用。采用实验处理增加GSH和氧化还原平衡以对抗老年Leydig因氧化应激造成睾酮下降，为预防和治疗Leydig老化提供最佳方案。

Leydig cells experience aging process, with the reduction of testosterone biosynthesis, thus adversely affecting the life quality of males, such as lower libido, osteoporosis, and diabetes. We hypothesize that age-related changes in the biology of Leydig cells result in the increased susceptibility of aged Leydig cells to acute oxidative stress, and therefore that aging poses a significant risk factor for the effects of environmental agents such as tert-butyl hydroperoxide and phthalates on these cells. Rats and transgenic mice （2 strains of γ-glutamylcysteine ligase and Nrf2 knockout mice）will be used to study consequences of age-related and experimentally-induced intracellular redox environment on Leydig cell susceptibility to acute oxidative stress; and the role of MAPK signaling. We will further determine the role of the Nrf2/Keap1 signaling system in regulating the alteration of the redox environment of aging Leydig cells, and thus cellular susceptibility to acute oxidative stress. Using experimental treatment to increase GSH and maintain the homeostasis of oxidation-reduction to antagonize age-related reduction of testosterone biosynthesis caused by oxidative stresses. This will provide an optimal protocol to prevent and treat Leydig cell aging.