Improving effects of telmisartan on spermatogenic disorder induced by fractionated low-dose irradiation in mice

Int Urol Nephrol. 2023 Jun;55(6):1427-1439. doi: 10.1007/s11255-023-03601-5. Epub 2023 Apr 24.

Abstract

Background: Male infertility is a hot problem worldwide, but there are few treatments, especially male infertility caused by irradiation is difficult to treat. The aim of this study was to investigate and evaluate novel drugs for the treatment of male infertility caused by irradiation.

Methods: we randomly divided 18 male BALB/c mice into 3 groups: control, irradiated, and telmisartan. Both irradiated and telmisartan group completed whole-body 0.5 Gy five times irradiation, and the telmisartan group received intraperitoneal injection of telmisartan (1.2 mg/kg) daily on the next day after irradiation, and all groups were sampled on day 25 after irradiation.

Results: Sperm motility results show that total sperm motility of irradiated group was significantly lower compared with control group, and testicular HE results showed that testis in irradiated group were severely damaged. Compared with irradiated group, the total sperm motility, sperm concentration, testicular index, Johnsen score, and the seminiferous tubule layer numbers were higher in telmisartan group (P < 0.05). The immunohistochemical staining showed γ-H2AX expression is higher in telmisartan group compared with irradiated group. And the relative mRNA expression of PLZF, GFRA1, STRA8, DMRT1, SPO11, SYCP2, OVOL2, CCNA1, TJP3, RUNX2, TXNDC2 TNP1, and PRM3 in telmisartan group was all significantly higher than irradiated group (P < 0.05).

Conclusion: In conclusion, in vivo experiments confirmed that telmisartan ameliorated the spermatogenic disorder in mice caused by fractionated low-dose irradiation via promoting spermatogenesis.

Keywords: Ionizing radiation; Spermatogenesis; Spermatogenic disorder; Telmisartan; Testis.

MeSH terms

  • Animals
  • DNA-Binding Proteins / metabolism
  • DNA-Binding Proteins / pharmacology
  • Humans
  • Infertility, Male* / drug therapy
  • Infertility, Male* / etiology
  • Male
  • Membrane Proteins / metabolism
  • Mice
  • Semen
  • Sperm Motility*
  • Spermatogenesis
  • Telmisartan / metabolism
  • Telmisartan / pharmacology
  • Testis / metabolism
  • Thioredoxins / metabolism
  • Thioredoxins / pharmacology
  • Transcription Factors / metabolism
  • Transcription Factors / pharmacology
  • Zonula Occludens Proteins / metabolism

Substances

  • Telmisartan
  • TXNDC2 protein, human
  • Membrane Proteins
  • Thioredoxins
  • Ovol2 protein, human
  • Transcription Factors
  • TJP3 protein, human
  • Zonula Occludens Proteins
  • Sycp2 protein, mouse
  • DNA-Binding Proteins