Qin Shaogang, Chi Xinyue, Zhu Zijian, Chen Chuanhe, Zhang Tuo, He Meina, Gao Meng, Zhao Ting, Zhang Jingwen, Zhang Lifan, Zheng Wenying, Chen Ziqi, Wang Wenji, Zhou Bo, Xia Guoliang, Wang Chao
State Key Laboratory of Farm Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing, China.
State Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, China.
Aging Cell. 2025 Jan;24(1):e14338. doi: 10.1111/acel.14338. Epub 2024 Sep 19.
Primordial follicles (PFs) function as the long-term reserve for female reproduction, remaining dormant in the ovaries and becoming progressively depleted with age. Oxidative stress plays an important role in promoting female reproductive senescence during aging, but the underlying mechanisms remain unclear. Here, we find that low levels of reactive oxygen species (ROS) are essential for sustaining PF dormancy. Compared to growing follicles, oocytes within PFs were shown to be more susceptible to ROS, which accumulates and damages PFs to promote reproductive senescence. Mechanistically, oocytes within PFs were shown to express high levels of the intracellular antioxidant enzyme superoxide dismutase 1 (SOD1), counteracting ROS accumulation. Decreased SOD1 expression, as a result of aging or through the experimental deletion of the Sod1 gene in oocytes, resulted in increased oxidative stress and triggered ferroptosis within PFs. In conclusion, this study identified antioxidant defense mechanisms protecting PFs in mouse ovaries and characterized cell death mechanisms of oxidative stress-induced PF death.
原始卵泡（PFs）作为雌性生殖的长期储备，在卵巢中保持休眠状态，并随着年龄的增长而逐渐消耗。氧化应激在衰老过程中促进雌性生殖衰老方面起着重要作用，但其潜在机制仍不清楚。在这里，我们发现低水平的活性氧（ROS）对于维持PF休眠至关重要。与生长中的卵泡相比，PF内的卵母细胞显示出对ROS更敏感，ROS积累并损害PF以促进生殖衰老。从机制上讲，PF内的卵母细胞显示出高水平表达细胞内抗氧化酶超氧化物歧化酶1（SOD1），以抵消ROS积累。由于衰老或通过实验性删除卵母细胞中的Sod1基因导致SOD1表达降低，导致氧化应激增加并引发PF内的铁死亡。总之，本研究确定了保护小鼠卵巢中PF的抗氧化防御机制，并表征了氧化应激诱导的PF死亡的细胞死亡机制。
