Chronic unpredictable stress induces anxiety-like behavior and oxidative stress, leading to diminished ovarian reserve
Abstract Chronic stress can adversely affect the female reproductive endocrine system, potentially leading to disorders and impairments in ovarian function. However, current research lacks comprehensive understanding regarding the biochemical characteristics and underlying mechanisms of ovarian dama...
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Nature Portfolio
2024-12-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-024-76717-y |
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| author | Zhihao Zhou Yangshuo Li Jie Ding Shuai Sun Wen Cheng Jin Yu Zailong Cai Zhexin Ni Chaoqin Yu |
| author_facet | Zhihao Zhou Yangshuo Li Jie Ding Shuai Sun Wen Cheng Jin Yu Zailong Cai Zhexin Ni Chaoqin Yu |
| author_sort | Zhihao Zhou |
| collection | DOAJ |
| description | Abstract Chronic stress can adversely affect the female reproductive endocrine system, potentially leading to disorders and impairments in ovarian function. However, current research lacks comprehensive understanding regarding the biochemical characteristics and underlying mechanisms of ovarian damage induced by chronic stress. We established a stable chronic unpredictable stress (CUS)-induced diminished ovarian reserve (DOR) animal model. Our findings demonstrated that prolonged CUS treatment over eight weeks resulted in increased atresia follicles in female mice. This atresia was accompanied by decreased AMH and increased FSH levels. Furthermore, we observed elevated levels of corticosterone both in the peripheral blood and within the ovary. Additionally, we detected abnormalities in ATP metabolism within the ovarian tissue. CUS exposure led to oxidative stress in the ovaries, fostering a microenvironment characterized by oxidative damage to mouse ovarian granulosa cells (mGCs) and heightened levels of reactive oxygen species. Furthermore, CUS prompted mGCs to undergo apoptosis via the mitochondrial pathway. These findings indicate a direct association between the fundamental physiological alterations leading to DOR and the oxidative phosphorylation processes within mGCs. The diminished ATP production by mGCs, triggered by CUS, emerges as a pivotal indicator of CUS-induced DOR. Our study establishes an animal model to investigate the impact of chronic stress on ovarian reserve function and sheds light on potential mechanisms underlying this phenomenon. |
| format | Article |
| id | doaj-art-6e43d0d9a67d483ea14da9a434563d1a |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-6e43d0d9a67d483ea14da9a434563d1a2024-12-29T12:15:35ZengNature PortfolioScientific Reports2045-23222024-12-0114111510.1038/s41598-024-76717-yChronic unpredictable stress induces anxiety-like behavior and oxidative stress, leading to diminished ovarian reserveZhihao Zhou0Yangshuo Li1Jie Ding2Shuai Sun3Wen Cheng4Jin Yu5Zailong Cai6Zhexin Ni7Chaoqin Yu8Department of Traditional Chinese Gynecology, The First Affiliated Hospital of Naval Military Medical University (Changhai Hospital)Department of Traditional Chinese Gynecology, The First Affiliated Hospital of Naval Military Medical University (Changhai Hospital)Department of Traditional Chinese Gynecology, The First Affiliated Hospital of Naval Military Medical University (Changhai Hospital)Department of Traditional Chinese Gynecology, The First Affiliated Hospital of Naval Military Medical University (Changhai Hospital)Department of Traditional Chinese Gynecology, The First Affiliated Hospital of Naval Military Medical University (Changhai Hospital)Department of Traditional Chinese Gynecology, The First Affiliated Hospital of Naval Military Medical University (Changhai Hospital)Department of Biochemistry and Molecular Biology, Naval Medical UniversityDepartment of Traditional Chinese Gynecology, The First Affiliated Hospital of Naval Military Medical University (Changhai Hospital)Department of Traditional Chinese Gynecology, The First Affiliated Hospital of Naval Military Medical University (Changhai Hospital)Abstract Chronic stress can adversely affect the female reproductive endocrine system, potentially leading to disorders and impairments in ovarian function. However, current research lacks comprehensive understanding regarding the biochemical characteristics and underlying mechanisms of ovarian damage induced by chronic stress. We established a stable chronic unpredictable stress (CUS)-induced diminished ovarian reserve (DOR) animal model. Our findings demonstrated that prolonged CUS treatment over eight weeks resulted in increased atresia follicles in female mice. This atresia was accompanied by decreased AMH and increased FSH levels. Furthermore, we observed elevated levels of corticosterone both in the peripheral blood and within the ovary. Additionally, we detected abnormalities in ATP metabolism within the ovarian tissue. CUS exposure led to oxidative stress in the ovaries, fostering a microenvironment characterized by oxidative damage to mouse ovarian granulosa cells (mGCs) and heightened levels of reactive oxygen species. Furthermore, CUS prompted mGCs to undergo apoptosis via the mitochondrial pathway. These findings indicate a direct association between the fundamental physiological alterations leading to DOR and the oxidative phosphorylation processes within mGCs. The diminished ATP production by mGCs, triggered by CUS, emerges as a pivotal indicator of CUS-induced DOR. Our study establishes an animal model to investigate the impact of chronic stress on ovarian reserve function and sheds light on potential mechanisms underlying this phenomenon.https://doi.org/10.1038/s41598-024-76717-yDiminished ovarian reserveAnxiety-like behaviorOvarian functionChronic unpredictable stressOxidative stressATP production |
| spellingShingle | Zhihao Zhou Yangshuo Li Jie Ding Shuai Sun Wen Cheng Jin Yu Zailong Cai Zhexin Ni Chaoqin Yu Chronic unpredictable stress induces anxiety-like behavior and oxidative stress, leading to diminished ovarian reserve Scientific Reports Diminished ovarian reserve Anxiety-like behavior Ovarian function Chronic unpredictable stress Oxidative stress ATP production |
| title | Chronic unpredictable stress induces anxiety-like behavior and oxidative stress, leading to diminished ovarian reserve |
| title_full | Chronic unpredictable stress induces anxiety-like behavior and oxidative stress, leading to diminished ovarian reserve |
| title_fullStr | Chronic unpredictable stress induces anxiety-like behavior and oxidative stress, leading to diminished ovarian reserve |
| title_full_unstemmed | Chronic unpredictable stress induces anxiety-like behavior and oxidative stress, leading to diminished ovarian reserve |
| title_short | Chronic unpredictable stress induces anxiety-like behavior and oxidative stress, leading to diminished ovarian reserve |
| title_sort | chronic unpredictable stress induces anxiety like behavior and oxidative stress leading to diminished ovarian reserve |
| topic | Diminished ovarian reserve Anxiety-like behavior Ovarian function Chronic unpredictable stress Oxidative stress ATP production |
| url | https://doi.org/10.1038/s41598-024-76717-y |
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