Reprod Toxicol. 2026 Oct 10:109376. doi: 10.1016/j.reprotox.2026.109376. Online ahead of print.
ABSTRACT
Over the years, evidence has begun to shed light on the influence of diets with high salt contents and increased dietary salt (NaCl) intake on ovarian damage and dysfunctions of female fertility. However, the mechanisms by which high dietary salt intake leads to ovarian dysfunction at the genetic and molecular levels remain largely unknown. This study investigated the impact of elevated NaCl concentrations on human granulosa cell metabolism, given their pivotal role in follicular development. We observed that exposure of human granulosa cell lines, KGN and SVOG, to high salt concentrations caused reductions in cell viability in a concentration-dependent manner. The results of metabolomics and transcriptomics analyses revealed significant enrichment of amino acid metabolism in KGN cells induced by high-salt treatment. Furthermore, exposure of KGN cells to 40 and 120mM NaCl resulted in an increase in the intracellular levels of most canonical amino acids as well as the expression of amino acid transporters. This was corroborated by western blotting, while Na+/K+-ATPase activity levels were significantly higher relative to untreated controls. Collectively, these findings demonstrate that exposure to elevated levels high salt concentrations have a marked influence on amino acid metabolism, which may have important implications for preventing ovarian dysfunction.
PMID:42858869 | DOI:10.1016/j.reprotox.2026.109376