Nme8 is essential for protection against chemotherapy drug cisplatin-induced male reproductive toxicity in mice
Cisplatin (CP), a chemotherapy drug commonly used in cancers treatment, causes serious reproductive toxicity. With younger cancer patients and increasing survival rates, it is important to preserve their reproductive capacity. NME8 is highly expressed in testis and contains thioredoxin and NDPK doma...
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Veröffentlicht in: | Cell death & disease 2024-10, Vol.15 (10), p.730-12, Article 730 |
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Sprache: | eng |
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Zusammenfassung: | Cisplatin (CP), a chemotherapy drug commonly used in cancers treatment, causes serious reproductive toxicity. With younger cancer patients and increasing survival rates, it is important to preserve their reproductive capacity. NME8 is highly expressed in testis and contains thioredoxin and NDPK domains, suggesting it may be a target against the CP-induced reproductive toxicity. We deleted exons 6–7 of the
Nme8
in mice based on human mutation sites and observed impaired transcript splicing. In mice,
Nme8
was not essential for spermatogenesis, possibly due to functional compensation by its paralog,
Nme5
.
Nme8
expression was elevated and translocated to the nucleus in response to two weeks of CP treatment. Under CP treatment,
Nme8
deficiency further impaired antioxidant capacity, induced lipid peroxidation and increased ROS level, and failed to activate autophagy, resulting in aggravated DNA damage in testes and sperm. Consequently, the proliferation and differentiation of spermatogonia and the meiosis of spermatocyte were almost completely halted, and sperm motility was impaired. Our research indicates that NME8 protects against CP-induced testis and sperm damage. This may provide new insights into the physiological functions of the
Nme
family and potential targets for preserving fertility in young male cancer patients. |
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ISSN: | 2041-4889 2041-4889 |
DOI: | 10.1038/s41419-024-07118-2 |