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Thiopurines exert harmful effects on spermatogenesis in Nudt15R138C knock-in mice.
- Source :
-
Journal of Gastroenterology . Feb2024, Vol. 59 Issue 2, p109-118. 10p. - Publication Year :
- 2024
-
Abstract
- Background: The association between thiopurine use and testicular reproductive functions remains unclear. In this study, we investigated whether thiopurines affect testicular functions based on the NUDT15 genotypes using Nudt15R138C knock-in mice. Methods: The male Nudt15R138C knock-in mice (9–12 weeks) were treated with mercaptopurine (MP: 0.5 mg/kg/day) for 4 or 12 weeks. To examine reversibility, some mice were maintained for a further 12 weeks under MP-free condition. Results: After MP treatment for 4 weeks, Nudt15R138C/R138C mice exhibited a significant reduction of testis weight compared to Nudt15+/+ mice and Nudt15+/R138C mice. The epithelial height and diameter of seminiferous tubules were significantly reduced in Nudt15R138C/R138C mice compared to Nudt15+/+ and Nudt15+/R138C mice. Apoptotic cells were significantly increased in Nudt15R138C/R138C mice, and most of apoptotic cells were spermatogonia. There were no significant changes in sperm counts and sperm morphology in MP-treated Nudt15R138C/R138C mice after 4-week MP treatment. On the other hand, after MP treatment for 12 weeks, the Nudt15+/R138C mice, but not Nudt15+/+ mice, exhibited a significant reduction in the testis weight and atrophic changes of seminiferous tubules, but these changes disappeared after 12-week rearing under MP-free condition. Despite a significant increase in abnormal sperm rate, there were no changes in the ability to conceive. No differences in serum levels of follicle-stimulating hormone or testosterone were observed between MP-treated Nudt15+/R138C and Nudt15+/+ mice after 12-week MP treatment. Conclusions: Thiopurines exert harmful effects on testicular reproductive function according to host NUDT15 genotypes. [ABSTRACT FROM AUTHOR]
- Subjects :
- *SPERMATOGENESIS
*SEMINIFEROUS tubules
*WEIGHT loss
*MICE
*TESTIS physiology
Subjects
Details
- Language :
- English
- ISSN :
- 09441174
- Volume :
- 59
- Issue :
- 2
- Database :
- Academic Search Index
- Journal :
- Journal of Gastroenterology
- Publication Type :
- Academic Journal
- Accession number :
- 175022110
- Full Text :
- https://doi.org/10.1007/s00535-023-02059-7