Dasatinib and quercetin increase testosterone and sperm concentration in mice

Physiol Int. 2023 May 26;110(2):121-134. doi: 10.1556/2060.2023.00192. Print 2023 Jun 12.

Abstract

Cellular senescence is a defense mechanism to arrest proliferation of damaged cells. The number of senescent cells increases with age in different tissues and contributes to the development of age-related diseases. Old mice treated with senolytics drugs, dasatinib and quercetin (D+Q), have reduced senescent cells burden. The aim of this study was to evaluate the effects of D+Q on testicular function and fertility of male mice. Mice (n = 9/group) received D (5 mg kg-1) and Q (50 mg kg-1) via gavage every moth for three consecutive days from 3 to 8 months of age. At 8 months mice were breed with young non-treated females and euthanized. The treatment of male mice with D+Q increased serum testosterone levels and sperm concentration and decreased abnormal sperm morphology. Sperm motility, seminiferous tubule morphometry, testicular gene expression and fertility were not affected by treatment. There was no effect of D+Q treatment in β-galactosidase activity and in lipofuscin staining in testes. D+Q treatment also did not affect body mass gain and testes mass. In conclusion, D+Q treatment increased serum testosterone levels and sperm concentration and decreased abnormal sperm morphology, however did not affect fertility. Further studies with older mice and different senolytics are necessary to elucidate the effects in the decline of sperm output (quality and quantity) associated with aging.

Keywords: Senotherapeutics; aging; cellular senescence; fertility; flavonoids.

MeSH terms

  • Animals
  • Dasatinib / pharmacology
  • Female
  • Male
  • Mice
  • Quercetin* / pharmacology
  • Semen / metabolism
  • Senotherapeutics
  • Sperm Motility
  • Spermatozoa
  • Testosterone*

Substances

  • Testosterone
  • Quercetin
  • Dasatinib
  • Senotherapeutics