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Autophagy participates in cyst breakdown and primordial folliculogenesis by reducing reactive oxygen species levels in perinatal mouse ovaries |
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| Authors: | Tu Zhihan Mu Xinyi Li Qingying Gao Rufei Zhang Yan Chen Xuemei Geng Yanqing Wang Yingxiong He Junlin |
| Affiliation: | 1. Laboratory of Reproductive Biology, College of Public Health and Administration, Chongqing Medical University, Chongqing, China Joint International Research Laboratory of Reproduction & Development, Chongqing Medical University, Chongqing, China Tu Zhihan and Mu Xinyi contributed equally to this work.;2. Laboratory of Reproductive Biology, College of Public Health and Administration, Chongqing Medical University, Chongqing, China Joint International Research Laboratory of Reproduction & Development, Chongqing Medical University, Chongqing, China Department of Histology and Embryology, College of Basic Medicine, Chongqing Medical University, Chongqing, China Tu Zhihan and Mu Xinyi contributed equally to this work.;3. Laboratory of Reproductive Biology, College of Public Health and Administration, Chongqing Medical University, Chongqing, China Joint International Research Laboratory of Reproduction & Development, Chongqing Medical University, Chongqing, China;4. Laboratory of Reproductive Biology, College of Public Health and Administration, Chongqing Medical University, Chongqing, China |
| Abstract: | 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, while N-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. |
| Keywords: | atophagy cysts breakdown primordial follicle assembly ROS |