Nme8, a member of the NME family of proteins, contains thioredoxin and NDPK domains. Some NME family proteins are involved in nucleoside diphosphate kinase (NDPK) function, and several isoforms including Nme8 exhibit 3'-5' exonuclease activity, suggesting roles in DNA proofreading and repair [2]. It has been associated with multiple biological processes and diseases, highlighting its overall biological importance. Genetic models, such as mouse models, can be valuable for studying its functions.

In mice, deletion of exons 6-7 of Nme8 based on human mutation sites led to impaired transcript splicing. Nme8 was not essential for spermatogenesis, likely due to functional compensation by its paralog, Nme5. However, Nme8 expression was elevated and translocated to the nucleus in response to two weeks of cisplatin (CP) treatment. Nme8 deficiency under CP treatment further impaired antioxidant capacity, induced lipid peroxidation, increased ROS level, failed to activate autophagy, and resulted in aggravated DNA damage in testes and sperm. This halted the proliferation and differentiation of spermatogonia, the meiosis of spermatocyte, and impaired sperm motility, indicating that NME8 protects against CP-induced testis and sperm damage [1].

In conclusion, Nme8 plays a crucial role in protecting against cisplatin-induced male reproductive toxicity. The gene knockout mouse model has been instrumental in revealing this function in the context of male reproductive health. Although Nme8 may not be essential for spermatogenesis on its own, it is vital in safeguarding the testes and sperm from the harmful effects of cisplatin treatment.