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Chronic stress induces meiotic arrest failure and ovarian reserve decline via the cAMP signaling pathway

Chronic stress is suspected to be a causal factor of female subfertility; however, the underlying mechanisms remain unclear. Here, we found that chronic stress inhibited the cyclic adenosine 3′,5′-monophosphate (cAMP) signaling pathway, leading to ovarian reserve decline in mice. A chronic stress mo...

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Detalles Bibliográficos
Autores principales: Jiang, Yiwen, Xu, Jing, Tao, Chengqiu, Lin, Yunying, Lin, Xiaoqi, Li, Ke, Liu, Qiyu, Saiyin, Hexige, Hu, Shuanggang, Yao, Guangxin, Sun, Yun, Zhang, Feng, Kang, Yu, Xu, Congjian, Zhang, Ling
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10499613/
https://www.ncbi.nlm.nih.gov/pubmed/37720535
http://dx.doi.org/10.3389/fendo.2023.1177061
Descripción
Sumario:Chronic stress is suspected to be a causal factor of female subfertility; however, the underlying mechanisms remain unclear. Here, we found that chronic stress inhibited the cyclic adenosine 3′,5′-monophosphate (cAMP) signaling pathway, leading to ovarian reserve decline in mice. A chronic stress model was constructed using restraint stress for 8 weeks. An elongated estrous cycle and a significant increase in the number of atretic follicles were observed in the stress group. We identified a significant increase in meiotic arrest failure (MAF) in oocytes in the stress group, characterized by condensed metaphase chromosomes, assembled spindles, or polar bodies in the oocytes. Whole-mount ovarian reserve estimation at the single-oocyte level using the CUBIC method (clear, unobstructed brain/body imaging cocktails and computational analysis) revealed a significant decrease in quiescent oocytes from 2,261/ovary in the control group to 1,373/ovary in the stress group. The number of growing oocytes also significantly decreased from 220/ovary in the control group to 150/ovary in the stress group. Real-time quantitative polymerase chain reaction (RT-qPCR) analysis of the meiotic arrest maintenance pathways revealed significant downregulation of Gpr3, Nppc, and Npr2 in the stress group. These results indicate that blocking cAMP production contributes to MAF and a decline in ovarian reserve. Overall, we present new insights into the mechanisms underlying chronic-stress-induced oocyte loss and potential targets for ovarian reserve preservation.