Exploring the Beneficial Effects of Se-Methylselenocysteine on GC-1/GC-2 Cells: From Cellular Uptake to Metabolic Pathway Regulation in Male Reproduction

Male infertility, a global health issue marked by spermatogenic failure, hinges on selenium (Se) as a key element for normal spermatogenesis. Among different Se species, Se-methylselenocysteine (MeSeCys) has been developed as a natural organic Se supplement with potent antioxidant and anti-inflammatory properties, but its direct effects on male reproduction need to be further explored. This study investigated the effect of MeSeCys on GC-1 spg (GC-1) and GC-2 spd (ts) (GC-2) cell lines, which mimic early stages. Treatment with 75 μmol/L MeSeCys for 24 h markedly enhanced the viability of both cell lines, with a more pronounced effect observed in GC-1 than in GC-2 cells. Moreover, this study demonstrated that MeSeCys enters cells through SLC7A11 or LRP8 channels and elevates intracellular Se levels in both GC-1 and GC-2 cells, with higher levels observed in GC-1 cells. RNA sequencing (RNA-seq) and bioinformatics analysis revealed that MeSeCys may regulate selenocompound metabolism and the glutathione metabolism pathway in both cell lines, increasing their intracellular glutathione (GSH) levels. Importantly, in GC-1 cells, MeSeCys specifically modulates the mTOR pathway, which further modulates glutathione metabolism and intracellular redox balance. This finding provides novel insights into the beneficial effects of MeSeCys on male reproductive cells, highlighting its potential as a nutritional supplement for male reproductive health.