Autophagy participates in cyst breakdown and primordial folliculogenesis by reducing reactive oxygen species levels in perinatal mouse ovaries.
Autophagy participates in cyst breakdown and primordial folliculogenesis by reducing reactive oxygen species levels in perinatal mouse ovaries.
复制标题
自噬通过降低围产期小鼠卵巢中的活性氧水平来参与囊肿破裂和原始卵泡发生。
DOI：
10.1002/jcp.27367
复制
发表时间：
2019
影响因子：
5.6
通讯作者：
Junlin He
中科院分区：
文献类型：
--
作者：
Zhihan Tu;Xinyi Mu;Qingying Li;Rufei Gao;Yan Zhang;Xuemei Chen;Yanqing Geng;Yingxiong Wang;Junlin He
小鼠出生后几天，原始卵泡的储备建立起来，为雌性生殖寿命中的所有卵母细胞提供服务。在这个过程中，超过一半的卵母细胞主要通过凋亡被淘汰。自噬是维持细胞内环境稳定的保守的细胞内过程，是卵母细胞存活的保护机制。在目前的研究中，我们推测自噬在原始卵泡发生中的新作用。在交配后16.5天至分娩后3天，在围产期卵巢中观察到活跃的自噬。3-甲基腺嘌呤（3-MA）对自噬的抑制增加了体内和器官培养中囊肿卵母细胞的数量，并延迟了卵泡形成。此外，活性氧（ROS）水平在3-MA处理的卵巢中升高，而氧化剂N-乙酰半胱氨酸减轻了3-MA对原始卵泡发生的抑制作用。此外，3‐MA处理后，调节卵泡活化的生长分化因子9和转化生长因子β1的表达降低。这些数据表明，生理水平的自噬在围产期卵巢调节生殖细胞囊肿破裂和原始卵泡组装ROS清除，并发挥广泛的影响，进一步卵泡发育。
The reserve of primordial follicles, which serves all oocytes for the female reproductive lifespan, is established a few days after birth in mice. During this process, more than half of the oocytes are primarily eliminated by apoptosis. Autophagy, the conserved intracellular process maintaining cellular homeostasis, serves as a protective mechanism for oocyte survival. In the current study, we speculate a new role for autophagy during primordial folliculogenesis. Active autophagy was observed in perinatal ovaries from 16.5 days post coitus to 3 days post parturition. The inhibition of autophagy by 3‐methyladenine (3‐MA) increased the number of cyst oocytes and delayed follicle formation in vivo and in organ cultures. Furthermore, the reactive oxygen species (ROS) level was elevated in ovaries treated with 3‐MA, whileN‐acetylcysteine, an oxidant, alleviated the inhibitory effect of 3‐MA on primordial folliculogenesis. Additionally, the expression of growth differentiation factor 9 and transforming growth factor β1, which regulates follicle activation, was decreased after 3‐MA treatment. These data suggest that the physiological level of autophagy in perinatal ovaries regulates germ cell cyst breakdown and primordial follicle assembly by ROS clearance and exerts extensive effects on further follicular development.