Berberine promotes primordial follicle activation and increases ovulated oocyte quantity in aged mice

Abstract Background Primordial follicle activation is vital for the reproduction of women with advanced age and premature ovarian insufficiency (POI). But there is a lack of effective and safe therapeutic options to activate their primordial follicles in vivo. Berberine (BBR) possesses multiple phar...

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Main Authors: Shuang Liu, Weiyong Wang, Huiyu Liu, Hongwei Wei, Yashuang Weng, Wenjun Zhou, Xiaodan Zhang, Sihui He, Ye Chen, Yahong Wang, Meijia Zhang, Xin Chen
Format: Article
Language:English
Published: BMC 2024-12-01
Series:Molecular Medicine
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Online Access:https://doi.org/10.1186/s10020-024-01042-z
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author Shuang Liu
Weiyong Wang
Huiyu Liu
Hongwei Wei
Yashuang Weng
Wenjun Zhou
Xiaodan Zhang
Sihui He
Ye Chen
Yahong Wang
Meijia Zhang
Xin Chen
author_facet Shuang Liu
Weiyong Wang
Huiyu Liu
Hongwei Wei
Yashuang Weng
Wenjun Zhou
Xiaodan Zhang
Sihui He
Ye Chen
Yahong Wang
Meijia Zhang
Xin Chen
author_sort Shuang Liu
collection DOAJ
description Abstract Background Primordial follicle activation is vital for the reproduction of women with advanced age and premature ovarian insufficiency (POI). But there is a lack of effective and safe therapeutic options to activate their primordial follicles in vivo. Berberine (BBR) possesses multiple pharmacological properties, but its impact on primordial follicle activation remains unclear. Methods The role of BBR on primordial activation was investigated by neonatal mouse ovary culture and intraperitoneal injection, and by human ovarian fragment culture. Furthermore, the effect of BBR on the quantity of ovulated oocytes was investigated by the intragastric administration of aged mice. Results BBR in vitro culture and in vivo intraperitoneal injection significantly increased growing follicle number and phosphorylated protein kinase B (p-Akt) levels in neonatal mouse ovaries. BBR also significantly increased the relative fluorescence intensities of p-Akt in the oocytes of primordial follicles. BBR-increased the number of growing follicles and the levels of p-Akt were blocked by LY294002, an inhibitor of phosphatidylinositol 3-kinase (PI3K). Furthermore, BBR intragastric administration significantly increased the quantity of ovulated oocytes in aged mice. Moreover, BBR significantly increased growing follicle proportion and p-Akt levels in cultured human ovarian fragments. Conclusion BBR promotes mouse and human primordial follicle activation through the PI3K/Akt pathway in oocytes, and improves the quantity of ovulated oocytes in aged mice. Our results suggest a potential use of oral medicine BBR to improve fertility in POI patients and aged women.
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spelling doaj-art-54f9aac0fd0445da9c2d68676eb07c102024-12-22T12:32:20ZengBMCMolecular Medicine1528-36582024-12-0130111310.1186/s10020-024-01042-zBerberine promotes primordial follicle activation and increases ovulated oocyte quantity in aged miceShuang Liu0Weiyong Wang1Huiyu Liu2Hongwei Wei3Yashuang Weng4Wenjun Zhou5Xiaodan Zhang6Sihui He7Ye Chen8Yahong Wang9Meijia Zhang10Xin Chen11The Innovation Centre of Ministry of Education for Development and Diseases, School of Medicine, South China University of TechnologyThe Innovation Centre of Ministry of Education for Development and Diseases, School of Medicine, South China University of TechnologyThe Innovation Centre of Ministry of Education for Development and Diseases, School of Medicine, South China University of TechnologyThe Innovation Centre of Ministry of Education for Development and Diseases, School of Medicine, South China University of TechnologyThe Innovation Centre of Ministry of Education for Development and Diseases, School of Medicine, South China University of TechnologyThe Innovation Centre of Ministry of Education for Development and Diseases, School of Medicine, South China University of TechnologyThe Innovation Centre of Ministry of Education for Development and Diseases, School of Medicine, South China University of TechnologyThe Innovation Centre of Ministry of Education for Development and Diseases, School of Medicine, South China University of TechnologyThe Innovation Centre of Ministry of Education for Development and Diseases, School of Medicine, South China University of TechnologyReproductive Medicine Center, Shunde Hospital of Southern Medical University (The First People’s Hospital of Shunde)The Innovation Centre of Ministry of Education for Development and Diseases, School of Medicine, South China University of TechnologyReproductive Medicine Center, Shunde Hospital of Southern Medical University (The First People’s Hospital of Shunde)Abstract Background Primordial follicle activation is vital for the reproduction of women with advanced age and premature ovarian insufficiency (POI). But there is a lack of effective and safe therapeutic options to activate their primordial follicles in vivo. Berberine (BBR) possesses multiple pharmacological properties, but its impact on primordial follicle activation remains unclear. Methods The role of BBR on primordial activation was investigated by neonatal mouse ovary culture and intraperitoneal injection, and by human ovarian fragment culture. Furthermore, the effect of BBR on the quantity of ovulated oocytes was investigated by the intragastric administration of aged mice. Results BBR in vitro culture and in vivo intraperitoneal injection significantly increased growing follicle number and phosphorylated protein kinase B (p-Akt) levels in neonatal mouse ovaries. BBR also significantly increased the relative fluorescence intensities of p-Akt in the oocytes of primordial follicles. BBR-increased the number of growing follicles and the levels of p-Akt were blocked by LY294002, an inhibitor of phosphatidylinositol 3-kinase (PI3K). Furthermore, BBR intragastric administration significantly increased the quantity of ovulated oocytes in aged mice. Moreover, BBR significantly increased growing follicle proportion and p-Akt levels in cultured human ovarian fragments. Conclusion BBR promotes mouse and human primordial follicle activation through the PI3K/Akt pathway in oocytes, and improves the quantity of ovulated oocytes in aged mice. Our results suggest a potential use of oral medicine BBR to improve fertility in POI patients and aged women.https://doi.org/10.1186/s10020-024-01042-zBerberinePrimordial follicle activationAktPremature ovarian insufficiency
spellingShingle Shuang Liu
Weiyong Wang
Huiyu Liu
Hongwei Wei
Yashuang Weng
Wenjun Zhou
Xiaodan Zhang
Sihui He
Ye Chen
Yahong Wang
Meijia Zhang
Xin Chen
Berberine promotes primordial follicle activation and increases ovulated oocyte quantity in aged mice
Molecular Medicine
Berberine
Primordial follicle activation
Akt
Premature ovarian insufficiency
title Berberine promotes primordial follicle activation and increases ovulated oocyte quantity in aged mice
title_full Berberine promotes primordial follicle activation and increases ovulated oocyte quantity in aged mice
title_fullStr Berberine promotes primordial follicle activation and increases ovulated oocyte quantity in aged mice
title_full_unstemmed Berberine promotes primordial follicle activation and increases ovulated oocyte quantity in aged mice
title_short Berberine promotes primordial follicle activation and increases ovulated oocyte quantity in aged mice
title_sort berberine promotes primordial follicle activation and increases ovulated oocyte quantity in aged mice
topic Berberine
Primordial follicle activation
Akt
Premature ovarian insufficiency
url https://doi.org/10.1186/s10020-024-01042-z
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