Early Consumption of Stevia rebaudiana Bertoni on Rat Females: Actions on Their Fertility, Progeny, and Behavior

Abstract

Background: The growing interest in healthy diets has led to increased consumption of natural products such as stevia. Pregnant females, who often consume high amounts of non-caloric sweeteners, are particularly vulnerable. Given the limited health guidelines on stevia, evaluating its effects on this population and their offspring is essential.

Objectives: This study assessed the impact of early, continuous exposure to an aqueous extract of Stevia rebaudiana Bertoni (Asteraceae) on female rat reproductive health, anxiety, sexual behavior, and progeny outcomes.

Methods: Female Sprague-Dawley rats (PND21) were assigned to a control group (CON, water) or a stevia group (STE). In experiment 1, estrous cycles were monitored via vaginal smears (CON, n = 6/assay; STE, n = 14/assay). Anxiety-like behavior was assessed using the elevated plus maze test, and sexual behavior was evaluated through the partner preference test (CON, n = 4/assay; STE, n = 4/assay). Pregnancy rate, duration, litter size, sex ratio, and offspring survival were also assessed. In experiment 2, stevia administration began 5, 10, 15, or 50 d before mating, and the same reproductive parameters were evaluated. Statistical analyses were performed using a Student's t-test, repeated measures analysis of variance (RM-ANOVA), and one-way analysis of variance (ANOVA) with Fisher's Protected Least Significant Difference post-hoc test.

Results: The STE group exhibited disrupted estrous cycles, reduced pregnancy rates, and smaller litters (with notably fewer males). Body weight was significantly lower in the STE group during the third week of pregnancy. There were no significant differences in food or beverage intake. Behaviorally, the STE group showed decreased sexual partner preference, lower anxiety, and increased risk assessment behavior. Prolonged premating exposure to stevia was associated with extended pregnancy duration, smaller litters, and higher pup weights at PND1.

Conclusions: Stevia disrupted fertility, reducing pregnancy rates, litter size, and male offspring, while extending gestation. Prolonged exposure worsened these effects, highlighting stevia's impact on reproduction and prenatal development. These findings underscore the need for improved health guidelines for vulnerable populations.

Keywords: Stevia rebaudiana; behavior; natural sweetener; non-caloric sweetener; progeny; reproduction.