Proanthocyanidins delaying the premature ovarian insufficiency through regulatory sirt1-p53-p21 signaling pathway in female germline stem cells
Abstract Background As women age, their ovarian follicle pool naturally declines. However, female germline stem cells (FGSCs) possess a unique ability to differentiate into oocytes and continuously self-renew, providing an effective means of delaying ovarian aging by replenishing the primordial foll...
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2025-05-01
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| Series: | Journal of Ovarian Research |
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| Online Access: | https://doi.org/10.1186/s13048-025-01661-y |
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| author | Wenbo Wu Mengying Bai Wenli Hong Shuyi Ling Yuan Li Yuqing Dai Ruoxin Weng Haifeng Wu Chongyang Ren Liujuan Zhang Ziqiong Zhou Zhisheng Zhong Xinxin Fu Yuehui Zheng |
| author_facet | Wenbo Wu Mengying Bai Wenli Hong Shuyi Ling Yuan Li Yuqing Dai Ruoxin Weng Haifeng Wu Chongyang Ren Liujuan Zhang Ziqiong Zhou Zhisheng Zhong Xinxin Fu Yuehui Zheng |
| author_sort | Wenbo Wu |
| collection | DOAJ |
| description | Abstract Background As women age, their ovarian follicle pool naturally declines. However, female germline stem cells (FGSCs) possess a unique ability to differentiate into oocytes and continuously self-renew, providing an effective means of delaying ovarian aging by replenishing the primordial follicle pool. Therefore, activating FGSCs is critical in reshaping and safeguarding ovarian function. Methods In this study, we investigated the biological activity of proanthocyanidins (PACs), natural antioxidants that exhibit anti-aging and anti-inflammatory properties beneficial for both male and female reproduction. Our in vivo and in vitro experiments demonstrate that PACs promote FGSCs proliferation while delaying ovarian aging. Results PACs increase the number of primordial follicles, primary follicles, corpus luteum while reducing cystic follicles, and elevate estradiol (E2) levels along with anti-mullerian hormone (AMH) concentration levels in mice. Additionally, PACs significantly boost FGSCs proliferation time- and dose-dependently by upregulating mRNA & protein expressions for FGSCs-specific markers such as MVH and OCT4 while downregulating p53/p21 via activation of silent information regulator 1(Sirt1) signaling pathway. The effects of PACs on FGCSs were found to be impeded by the Sirt1 inhibitor EX527. Conclusion PACS delay premature ovarian insufficiency (POI) through regulating the Sirt1-p53-p21 signaling pathway involving FGSCs. |
| format | Article |
| id | doaj-art-69f60b9fa5474fbea708bcadcc664566 |
| institution | Kabale University |
| issn | 1757-2215 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Ovarian Research |
| spelling | doaj-art-69f60b9fa5474fbea708bcadcc6645662025-08-20T03:53:13ZengBMCJournal of Ovarian Research1757-22152025-05-0118111210.1186/s13048-025-01661-yProanthocyanidins delaying the premature ovarian insufficiency through regulatory sirt1-p53-p21 signaling pathway in female germline stem cellsWenbo Wu0Mengying Bai1Wenli Hong2Shuyi Ling3Yuan Li4Yuqing Dai5Ruoxin Weng6Haifeng Wu7Chongyang Ren8Liujuan Zhang9Ziqiong Zhou10Zhisheng Zhong11Xinxin Fu12Yuehui Zheng13The Fourth Clinical Medical College of Guangzhou University of Traditional Chinese Medicine, Shenzhen Traditional Chinese Medicine HospitalThe Fourth Clinical Medical College of Guangzhou University of Traditional Chinese Medicine, Shenzhen Traditional Chinese Medicine HospitalThe Fourth Clinical Medical College of Guangzhou University of Traditional Chinese Medicine, Shenzhen Traditional Chinese Medicine HospitalThe Fourth Clinical Medical College of Guangzhou University of Traditional Chinese Medicine, Shenzhen Traditional Chinese Medicine HospitalThe Fourth Clinical Medical College of Guangzhou University of Traditional Chinese Medicine, Shenzhen Traditional Chinese Medicine HospitalThe Fourth Clinical Medical College of Guangzhou University of Traditional Chinese Medicine, Shenzhen Traditional Chinese Medicine HospitalThe Fourth Clinical Medical College of Guangzhou University of Traditional Chinese Medicine, Shenzhen Traditional Chinese Medicine HospitalThe Fourth Clinical Medical College of Guangzhou University of Traditional Chinese Medicine, Shenzhen Traditional Chinese Medicine HospitalThe Fourth Clinical Medical College of Guangzhou University of Traditional Chinese Medicine, Shenzhen Traditional Chinese Medicine HospitalThe Fourth Clinical Medical College of Guangzhou University of Traditional Chinese Medicine, Shenzhen Traditional Chinese Medicine HospitalThe Fourth Clinical Medical College of Guangzhou University of Traditional Chinese Medicine, Shenzhen Traditional Chinese Medicine HospitalThe Fourth Clinical Medical College of Guangzhou University of Traditional Chinese Medicine, Shenzhen Traditional Chinese Medicine HospitalDepartment of National Demonstration Center for Clinical Teaching &Training, School of Medicine, Xiang’an Hospital of Xiamen University, Xiamen UniversityThe Fourth Clinical Medical College of Guangzhou University of Traditional Chinese Medicine, Shenzhen Traditional Chinese Medicine HospitalAbstract Background As women age, their ovarian follicle pool naturally declines. However, female germline stem cells (FGSCs) possess a unique ability to differentiate into oocytes and continuously self-renew, providing an effective means of delaying ovarian aging by replenishing the primordial follicle pool. Therefore, activating FGSCs is critical in reshaping and safeguarding ovarian function. Methods In this study, we investigated the biological activity of proanthocyanidins (PACs), natural antioxidants that exhibit anti-aging and anti-inflammatory properties beneficial for both male and female reproduction. Our in vivo and in vitro experiments demonstrate that PACs promote FGSCs proliferation while delaying ovarian aging. Results PACs increase the number of primordial follicles, primary follicles, corpus luteum while reducing cystic follicles, and elevate estradiol (E2) levels along with anti-mullerian hormone (AMH) concentration levels in mice. Additionally, PACs significantly boost FGSCs proliferation time- and dose-dependently by upregulating mRNA & protein expressions for FGSCs-specific markers such as MVH and OCT4 while downregulating p53/p21 via activation of silent information regulator 1(Sirt1) signaling pathway. The effects of PACs on FGCSs were found to be impeded by the Sirt1 inhibitor EX527. Conclusion PACS delay premature ovarian insufficiency (POI) through regulating the Sirt1-p53-p21 signaling pathway involving FGSCs.https://doi.org/10.1186/s13048-025-01661-yProanthocyanidinsFemale germline stem cellsSilent information regulator 1Premature ovarian insufficiencyMice |
| spellingShingle | Wenbo Wu Mengying Bai Wenli Hong Shuyi Ling Yuan Li Yuqing Dai Ruoxin Weng Haifeng Wu Chongyang Ren Liujuan Zhang Ziqiong Zhou Zhisheng Zhong Xinxin Fu Yuehui Zheng Proanthocyanidins delaying the premature ovarian insufficiency through regulatory sirt1-p53-p21 signaling pathway in female germline stem cells Journal of Ovarian Research Proanthocyanidins Female germline stem cells Silent information regulator 1 Premature ovarian insufficiency Mice |
| title | Proanthocyanidins delaying the premature ovarian insufficiency through regulatory sirt1-p53-p21 signaling pathway in female germline stem cells |
| title_full | Proanthocyanidins delaying the premature ovarian insufficiency through regulatory sirt1-p53-p21 signaling pathway in female germline stem cells |
| title_fullStr | Proanthocyanidins delaying the premature ovarian insufficiency through regulatory sirt1-p53-p21 signaling pathway in female germline stem cells |
| title_full_unstemmed | Proanthocyanidins delaying the premature ovarian insufficiency through regulatory sirt1-p53-p21 signaling pathway in female germline stem cells |
| title_short | Proanthocyanidins delaying the premature ovarian insufficiency through regulatory sirt1-p53-p21 signaling pathway in female germline stem cells |
| title_sort | proanthocyanidins delaying the premature ovarian insufficiency through regulatory sirt1 p53 p21 signaling pathway in female germline stem cells |
| topic | Proanthocyanidins Female germline stem cells Silent information regulator 1 Premature ovarian insufficiency Mice |
| url | https://doi.org/10.1186/s13048-025-01661-y |
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