Senolytic treatment fails to improve ovarian reserve or fertility in female mice.

Autor: Garcia DN; Faculdade de Nutrição, Universidade Federal de Pelotas, Rua Gomes Carneiro, 1 - Sala 239, Pelotas, RS, CEP 96010-610, Brazil., Hense JD; Faculdade de Nutrição, Universidade Federal de Pelotas, Rua Gomes Carneiro, 1 - Sala 239, Pelotas, RS, CEP 96010-610, Brazil., Zanini BM; Faculdade de Nutrição, Universidade Federal de Pelotas, Rua Gomes Carneiro, 1 - Sala 239, Pelotas, RS, CEP 96010-610, Brazil., Isola JVV; Aging & Metabolism Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA., Prosczek JB; Faculdade de Nutrição, Universidade Federal de Pelotas, Rua Gomes Carneiro, 1 - Sala 239, Pelotas, RS, CEP 96010-610, Brazil., Ashiqueali S; College of Medicine, Burnett School of Biomedical Sciences, University of Central Florida, Orlando, FL, USA., Oliveira TL; Centro de Biotecnologia, Universidade Federal de Pelotas, Pelotas, RS, Brazil., Mason JB; College of Veterinary Medicine, Department of Veterinary Clinical and Life Sciences, Center for Integrated BioSystems, Utah State University, Logan, UT, USA., Schadock IC; Experimental Toxicology Department, German Institute for Risk Assessment, Berlin, Germany., Barros CC; Faculdade de Nutrição, Universidade Federal de Pelotas, Rua Gomes Carneiro, 1 - Sala 239, Pelotas, RS, CEP 96010-610, Brazil., Stout MB; College of Medicine, Burnett School of Biomedical Sciences, University of Central Florida, Orlando, FL, USA., Masternak MM; College of Medicine, Burnett School of Biomedical Sciences, University of Central Florida, Orlando, FL, USA.; Department of Head and Neck Surgery, Poznan University of Medical Sciences, Poznan, Poland., Schneider A; Faculdade de Nutrição, Universidade Federal de Pelotas, Rua Gomes Carneiro, 1 - Sala 239, Pelotas, RS, CEP 96010-610, Brazil. augusto.schneider@ufpel.edu.br.
Jazyk: angličtina
Zdroj: GeroScience [Geroscience] 2024 Jun; Vol. 46 (3), pp. 3445-3455. Date of Electronic Publication: 2024 Feb 15.
DOI: 10.1007/s11357-024-01089-0
Abstrakt: Senescent cell number increases with age in different tissues, leading to greater senescent cell load, proinflammatory stress, and tissue dysfunction. In the current study, we tested the efficacy of senolytic drugs to reduce ovarian senescence and improve fertility in reproductive age female mice. In the first experiment, 1-month-old C57BL/6 female mice were treated every other week with D + Q (n = 24) or placebo (n = 24). At 3 and 6 months of age, female mice were mated with untreated males to evaluate pregnancy rate and litter size. In the second experiment, 6-month-old C57BL/6 female mice were treated monthly with D + Q (n = 30), fisetin (n = 30), or placebo (n = 30). Females were treated once a month until 11 months of age, then they were mated with untreated males for 30 days to evaluate pregnancy rate and litter size. In the first experiment, D + Q treatment did not affect pregnancy rate (P = 0.68), litter size (P = 0.58), or ovarian reserve (P > 0.05). Lipofuscin staining was lower in females treated with D + Q (P = 0.04), but expression of senescence genes in ovaries was similar. In the second experiment, D + Q or fisetin treatment also did not affect pregnancy rate (P = 0.37), litter size (P = 0.20), or ovarian reserve (P > 0.05). Lipofuscin staining (P = 0.008) and macrophage infiltration (P = 0.002) was lower in fisetin treated females. Overall, treatment with D + Q or fisetin did not affect ovarian reserve or fertility but did decrease some senescence markers in the ovary.
(© 2024. The Author(s), under exclusive licence to American Aging Association.)
Databáze: MEDLINE
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