Protective effect of nicotinamide mononucleotide against soybean isoflavone induced damage in mouse testis

Soybean isoflavone (SI) was one type of phytoestrogen that competitively interacts with estrogen in the body, potentially interfering with endocrine balance, spermatogenesis, and the normal function of testicular cells. Nicotinamide mononucleotide (NMN), an important bioactive substance, enhances organ and tissue function through mechanisms such as reducing oxidative stress. However, limited information exists regarding the ability of NMN to improve phytoestrogen-induced damage to testis development in mice. The study investigated the protective effect of NMN on testicular damage in mice caused by SI. The results of this study revealed SI-treated mice exhibited a significant reduction in body weight, testicular index, and reproduction-related factors, as well as a marked increase in apoptosis. RNA sequencing (RNA-seq) results demonstrated that exposure to SI led to the enrichment of differentially expressed genes (DEGs) primarily in cellular autophagy and proliferation pathways within mouse testicular tissues. Administration of SI at doses of 200 mg/kg and 400 mg/kg downregulated the Rb1cc1 gene in the longevity-regulating pathway and the Vav2 gene in the cAMP signaling pathway in mouse testes. In contrast, treatment with 100 mg/kg NMN significantly alleviated the adverse effects induced by SI. In summary, NMN exhibited significant therapeutic potential in alleviating SI-induced testicular damage.