Effects of daily exposure to saccharin sodium and rebaudioside A on the ovarian cycle and steroidogenesis in rats

Saccharin sodium and rebaudioside A are widely used as non-caloric sweeteners in our daily life; however, the impacts and regulatory mechanisms of such sweeteners on reproduction remain unclear. In the present study, we used rats as animal models to evaluate the effects of daily exposure to saccharin sodium and rebaudioside A on ovarian biologic functions. Weanling rats were distributed into five experimental groups receiving normal water, 1.5 or 7.5 mM saccharin sodium solution, or 0.5 or 2.5 mM rebaudioside A solution for 48 days of exposure. The results showed an increased percentage of abnormal estrous cycles, augmented number of ovarian cysts, elevated serum progesterone levels, and increased expression of steroidogenesis-related factors in saccharin sodium-treated groups. Conversely, rebaudioside A-treated groups showed decreased serum progesterone levels. Our findings suggest that saccharin sodium exerts adverse biologic effects on ovaries, and rebaudioside A is a potential steroidogenic disruptor in female rats.