Celastrol modulates IRS1 expression to alleviate ovarian aging and to enhance follicular development
文献类型： 外文期刊
作者： Jiang, Yao 1 ; Shi, Yonghua 3 ; Lv, Meng 3 ; Wang, Tao 5 ; Wang, Penghao 1 ; Yuan, Xiaolong 1 ; Gao, Fei 7 ; Ma, Bin 1 ;
作者机构： 1.Murdoch Univ, Sch Med Mol & Forens Sci, Murdoch, WA, Australia
2.Murdoch Univ, Hlth Futures Inst, Ctr Hlth Ageing, Murdoch, WA, Australia
3.South China Agr Univ, State Key Lab Swine & Poultry Breeding Ind, Natl Engn Res Ctr Breeding Swine Ind,Guangdong Pro, Coll Anim Sci,Guangdong Lab Lingnan Modern Agr, Guangzhou, Guangdong, Peoples R China
4.Sun Yat Sen Univ, Canc Ctr, Zhongshan, Guangdong, Peoples R China
5.Kids Res Inst Australia, Nedlands, WA, Australia
6.Murdoch Univ, Food Future Inst, Ctr Crop & Food Innovat, Murdoch, WA, Australia
7.Chinese Acad Agr Sci, Guangdong Lab Lingnan Modern Agr, Agr Genom Inst Shenzhen,Minist Agr, Shenzhen Branch,Genome Anal Lab, Shenzhen, Guangdong, Peoples R China
关键词： Celastrol; IRS1; Ovarian aging; Oocyte maturation; Follicular development; Natural product
期刊名称：CELL BIOLOGY AND TOXICOLOGY （ 影响因子：5.9； 五年影响因子：6.1 ）
ISSN： 0742-2091
年卷期： 2025 年 41 卷 1 期
页码：
收录情况： SCI
摘要： 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.
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