Influences of non‐nutritive sweeteners on ovarian and uterine expression of T1R2 and T1R3 in peripubertal female guinea pigs

The underlying mechanism of taste receptor type 1 subunit 2 (T1R2) and taste receptor type 1 subunit 3 (T1R3) in the hormonal and reproductive system is still elusive. A low or a high dose of sweetness equivalent to that sodium saccharin (SS, 1.5 or 7.5 mM) and rebaudioside A (RA, 0.5 or 2.5 mM) was administered to young female guinea pigs for 28 consecutive days from the age of 28 days. Our results indicated that the sweet taste receptor subunit T1R2 was markedly expressed in the ovary and uterus of guinea pigs, whereas the T1R3 protein was expressed at a lower level. We elucidated that low-dose (1.5 mM) SS increased body and ovary weight associated with elevated ovarian expression of T1R2 in guinea pigs, unlike the high-dose (7.5 mM) SS, which suppressed the ovarian expression of T1R2 and resulted in certain adverse effects on ovarian and uterine morphology. Furthermore, high-dose (2.5 mM) RA increased the number of corpus luteum and elevated uterine expression of T1R2, whereas low-dose (0.5 mM) RA induced increased secretion of serum progesterone. Therefore, our findings suggest that we should pay more attention to the potential adverse effects, including increases in ovary weight, morphology changes, and increased progesterone that result from the dose-dependent regulation of T1R2 by non-nutritive sweeteners (NNS) in the ovaries and uteri of peripubertal females.