Nicotinamide mononucleotide ameliorates impaired testicular spermatogenesis in uranium-exposed mice by modulating glycolytic pathways.

Natural uranium is a ubiquitous element in the environment, and human exposure to low levels of uranium is unavoidable. Several concerns have recently been raised about the reproductive effects of chronic exposure to low levels of uranium. Therefore, the aim of this study was to investigate the protective effect of Nicotinamide mononucleotide（NMN） on uranium exposure-induced testicular sperm function in mice. To this end, a research model was established in which testicular damage and spermatogenic dysfunction were induced in adult male mice by intraperitoneal injection of two different doses of uranyl nitrate. Following a week of intraperitoneal injection, the mice were given oral doses of 500 mg/kg of NMN, a dose that was validated in an in vitro cellular model. The results demonstrated a decline in testicular weight and epididymis weight, along with a reduction in sperm count, in comparison to the control group. Subsequent observation of testicular morphology revealed the presence of disorganized seminiferous tubules, characterized by reduced area and diameter. Concurrently, a downregulation of the anti-apoptotic factor (Bcl-2) and an upregulation of the apoptotic factor (Bax) were observed in the testis. Furthermore, an analysis of testicular genetic expression levels of Sertoli cell (SCs) markers (WT-1, Sox9, PCNA, and Vimentin) revealed a substantial exacerbation of pathological changes, including an augmentation in the severity of tubular degeneration. NMN treatment resulted in a significant enhancement of testicular function, as evidenced by an increase in epididymal and testicular weights, as well as sperm counts, when compared to saline-treated uranium-exposed mice.