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CC BY V4.0, Open Access
Journal article
Celastrol modulates IRS1 expression to alleviate ovarian aging and to enhance follicular development
Cell biology and toxicology, Vol.41(1), 129
2025
Abstract
Ovarian aging significantly contributes to the decline of the female reproductive system, adversely affecting fertility and endocrine homeostasis. To address the challenges posed by reproductive aging, natural products have shown promising preventive and therapeutic effects. Here, we investigated the beneficial effects of natural compound celastrol on ovarian development and aging, together with its underlying mechanisms. We found that celastrol administration at a concentration of 3 mg/kg promoted follicle development in young mice and enhanced porcine oocyte maturation, while regulating granulosa cell proliferation and apoptosis. In 12-month-old mice (equivalent to middle-aged adults), celastrol exhibited similar beneficial effects. Transcriptomic analysis revealed that differentially expressed genes post-celastrol treatment were associated with steroid biosynthesis, estrogen signaling pathways, type 2 diabetes, insulin secretion, meiosis, and apoptosis. Additionally, insulin receptor substrate 1 (IRS1), an adapter protein in insulin signaling, was shown to advance puberty in young mice and to facilitate oocyte maturation. Overexpression of IRS1 in oocytes promoted follicular development and oocyte maturation, resulting in enhanced steroid hormone levels, whereas IRS1 knockdown inhibited these processes. Our findings indicate that celastrol may regulate ovarian development and aging by modulating IRS1 expression and its related pathways, suggesting celastrol as a novel small-molecule compound targeting IRS1, and offering new perspectives for potential therapeutic strategies against reproductive aging and infertility.
Details
- Title
- Celastrol modulates IRS1 expression to alleviate ovarian aging and to enhance follicular development
- Authors/Creators
- Yao Jiang - Murdoch UniversityYonghua Shi - Agricultural Genomics Institute at ShenzhenMeng Lv - South China Agricultural UniversityTao Wang - The University of MelbournePenghao Wang - Murdoch University, Centre for Crop and Food InnovationXiaolong Yuan - South China Agricultural UniversityFei Gao - Agricultural Genomics Institute at ShenzhenBin Ma - Murdoch University, School of Medical, Molecular and Forensic Sciences
- Publication Details
- Cell biology and toxicology, Vol.41(1), 129
- Publisher
- Springer Netherlands
- Grant note
- 2024B03J1305 / Science and Technology Project of Guangzhou 2024B1515020112, 2024A1515012999, and 2023A1515030054; 2024B1515020112, 2024A1515012999, and 2023A1515030054 / Guangdong Basic and Applied Basic Research Foundation 2022-4408X1-43010402-0019 / Breed Industry Innovation Park of Guangdong Xiaoerhua Pig Murdoch University
- Identifiers
- 991005810050107891
- Copyright
- © The Author(s) 2025
- Murdoch Affiliation
- Centre for Crop and Food Innovation; Centre for Healthy Ageing; School of Medical, Molecular and Forensic Sciences
- Language
- English
- Resource Type
- Journal article
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