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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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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
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author 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
author_facet 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
author_sort Jiang, Yiwen
collection PubMed
description 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.
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spelling pubmed-104996132023-09-15 Chronic stress induces meiotic arrest failure and ovarian reserve decline via the cAMP signaling pathway 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 Front Endocrinol (Lausanne) Endocrinology 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. Frontiers Media S.A. 2023-08-30 /pmc/articles/PMC10499613/ /pubmed/37720535 http://dx.doi.org/10.3389/fendo.2023.1177061 Text en Copyright © 2023 Jiang, Xu, Tao, Lin, Lin, Li, Liu, Saiyin, Hu, Yao, Sun, Zhang, Kang, Xu and Zhang https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Endocrinology
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
Chronic stress induces meiotic arrest failure and ovarian reserve decline via the cAMP signaling pathway
title Chronic stress induces meiotic arrest failure and ovarian reserve decline via the cAMP signaling pathway
title_full Chronic stress induces meiotic arrest failure and ovarian reserve decline via the cAMP signaling pathway
title_fullStr Chronic stress induces meiotic arrest failure and ovarian reserve decline via the cAMP signaling pathway
title_full_unstemmed Chronic stress induces meiotic arrest failure and ovarian reserve decline via the cAMP signaling pathway
title_short Chronic stress induces meiotic arrest failure and ovarian reserve decline via the cAMP signaling pathway
title_sort chronic stress induces meiotic arrest failure and ovarian reserve decline via the camp signaling pathway
topic Endocrinology
url 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
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