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The senolytic drug ABT-263 accelerates ovarian aging in older female mice.
- Source :
-
Scientific reports [Sci Rep] 2024 Oct 05; Vol. 14 (1), pp. 23178. Date of Electronic Publication: 2024 Oct 05. - Publication Year :
- 2024
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Abstract
- Previous studies have reported that senolytic drugs can reverse obesity-mediated accumulation of senescent cells in the ovary and protect against cisplatin-induced ovarian injury by removing senescent cells. Early intervention with ABT-263 has been shown to mitigate ovarian aging. However, it remains unknown whether treatment with ABT-263 could rejuvenate the aged ovary in reproductively old females. Therefore, the current study was aimed to investigate whether advanced age intervention with ABT-263 could ameliorate age-related decline in ovarian function. Fourteen 16-month-old mice with a C57/BL6 background were treated with ABT-263 (Nā=ā7) or vehicle (Nā=ā7) for two weeks. Mice were initially treated with ABT-263 (60 mg/kg/d) or vehicle for 7 consecutive days. After a 7-day break, the treatment was repeated for another 7 consecutive days. Six 2-month-old mice with C57BL/6 were used as a young control. The hormonal levels, estrus cycles, ovarian reserve, ovarian cell proliferation and apoptosis, ovarian fibrosis, and steroidogenic gene expression of ovarian stromal cells were evaluated. ABT-263 treatment did not rescue abnormal estrus cycles and sex hormonal levels, or inhibit the formation of multinucleated giant cells and ovarian stromal cell apoptosis in aged ovaries. However, it reduced ovarian fibrosis and preserved the steroidogenic gene expression of ovarian stromal cells in aged ovaries. Importantly, ABT-263 treatment further depleted ovarian follicles in aged mice. In conclusion, ABT-263 treatment accelerated the depletion of ovarian follicles in aged mice, suggesting that senolytic drugs for reproductively old female may adversely affect female fertility.<br /> (© 2024. The Author(s).)
- Subjects :
- Animals
Female
Mice
Senotherapeutics pharmacology
Cell Proliferation drug effects
Ovarian Reserve drug effects
Estrous Cycle drug effects
Cellular Senescence drug effects
Stromal Cells metabolism
Stromal Cells drug effects
Ovary drug effects
Ovary metabolism
Ovary pathology
Sulfonamides pharmacology
Aging drug effects
Mice, Inbred C57BL
Aniline Compounds pharmacology
Apoptosis drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 2045-2322
- Volume :
- 14
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Scientific reports
- Publication Type :
- Academic Journal
- Accession number :
- 39369073
- Full Text :
- https://doi.org/10.1038/s41598-024-73828-4