Effects of non-nutritive sweeteners on the sweet taste receptor expression and reproductive function in female guinea pigs

Non-nutritive sweeteners (NNS) are widely used food additives with unclear reproductive effects. This study examined how dietary NNS supplementation affects taste receptors T1R2/T1R3 expression in female guinea pig reproductive organs. Four groups of ten animals either received the control (basal diet) or basal diet supplemented with either rebaudioside A (RA, 330 mg/kg), saccharin sodium (SS, 800 mg/kg), or sucralose (TGS, 167 mg/kg) for 28 consecutive days. All NNS significantly increased serum progesterone and estradiol levels (P < 0.05). RA significantly upregulated ovarian T1R2/T1R3 expression (P < 0.05), while SS and TGS groups showed higher incidence of follicular cysts and structural disorganization. In uterine tissues, T1R2 expression was significantly higher in TGS and SS groups compared to control and RA groups (P < 0.05), while T1R3 expression was significantly elevated in the SS group compared to all others (P < 0.05). Our findings suggest that dietary NNS supplementation induces ovarian histological alterations, activates sweet taste receptors in reproductive tissues, and elevates serum P₄ and E₂ levels, indicating potential risks to female reproductive health through sweet taste receptor-mediated modulation of steroidogenesis and disruption of follicular development.