Influences of non-nutritive sweeteners on sweet taste receptors and reproductive hormone signaling in guinea pigs.

Non-nutritive sweeteners (NNS) are widespread in the food industry, but their effects on reproductive endocrine function remain inadequately characterized within the current scientific literature. This study investigated NNS impacts on hypothalamic-pituitary-ovarian (HPO) axis function in guinea pigs. The results showed that the NNS groups exhibited significantly lower serum levels of gonadotropin-releasing hormone (GnRH) and follicle-stimulating hormone (FSH) compared to controls, with rebaudioside A (RA) showing the lowest GnRH. Conversely, luteinizing hormone (LH) concentrations were significantly elevated in NNS groups. The RA group exhibited increased testosterone (T) levels, and all experimental groups showed more SS follicular cysts. T1R2 protein expression was highest in the sucralose (TGS) group, while gonadotropin-releasing hormone receptor (GnRHR) expression decreased significantly in NNS groups, particularly with RA. Luteinizing hormone receptor (LHR) protein expression increased significantly in NNS groups, with no changes in follicle-stimulating hormone receptor (FSHR) or T1R3 expression. Therefore, NNS supplementation affects HPO axis function in guinea pigs, as evidenced by decreased serum GnRH and FSH levels, increased LH content, inhibited GnRHR protein expression, and promoted LHR protein expression. The observed upregulation of T1R2 protein expression in the TGS group suggests a potential link between sweet taste receptor activation and reproductive hormone regulation.