(116) Effects of Chronic Maternal Exposure to Propylparaben on Reproduction in Murine Offspring

Swarna Pal Tisha, Jie Li, and Ayelet Ziv-Gal 

Department of Comparative Biosciences, University of Illinois at Urbana-Champaign, Urbana, Illinois

 

Abstract Text:

Parabens are antimicrobial chemicals extensively used as preservatives in cosmetics, food products, and pharmaceuticals. They are consistently detected in biological samples, including urine samples of pregnant women, and can cross the placenta. This is concerning because the limited available studies suggest that parabens are endocrine disruptors and thus may potentially have long-term effects on offspring. Propylparaben is one of the most used parabens, yet its impact on female reproduction is mostly unknown. In the current study, we hypothesized that maternal chronic exposure to propylparaben, at human-relevant doses, would alter reproduction of the female offspring (F1). To test this hypothesis, 3-month-old female CD-1 mice were treated daily with propylparaben (2 µg/kg, 20 µg/kg, or 200 µg/kg) for six months. The females were then mated with unexposed male breeders. Following weaning, female offspring were kept and at the age of 3 months were subjected to continuous breeding study over seven consecutive births cycles (n = 4-7 per group). At the end of the last breeding cycle, estrous cyclicity was evaluated over 18 days to determine the time spent in each estrous stage. Reproductive outcomes included time between births, litter size, mean pup weight, and percent live pups on postnatal days (PND) 0 and 3. The statistical analysis in SAS employed mixed models to examine the effects of treatment, estrous stage, and breeding cycles, with mouse as a random effect to account for repeated measures. Tukey’s HSD was used for post-hoc comparisons, and log-logit transformations were applied for proportions. Repeated measures were handled using AR(1) and CS correlation structures, and adjustments for multiple testing were made in the comparisons. A p-value of ≤0.05 was considered statistically significant. Estrous cyclicity evaluation indicate that although the total number of days spent in each estrous cycle stage was comparable between groups, a significant interaction between ‘treatment’ and ‘estrous stage’ suggests a stage-specific effect of PP exposure on estrous cycle duration. Specifically, females exposed to PP at 20 µg/kg tended to spend more time in diestrus (mean±SEM, 15.0±1.1 days), whereas those exposed to 200 µg/kg spent less time in diestrus (9.0±1.0 days) compared to controls (12.1±0.8 days). Reproductive outcomes, including ‘time between births’ and ‘percent live pups’ on PND0 or PND3 were similar across treatment groups, regardless of the breeding cycle. While total average litter size remained comparable between groups, a significant interaction between ‘treatment’ and ‘breeding cycle’ indicates a group-specific effect on litter size over time. Specifically, females exposed to PP at 200 µg/kg tended to have smaller litters, particularly from the fifth breeding cycle onward. Additionally, ‘mean pup weight’ on PND0 showed a tendency to increase across breeding cycles in the 200 µg/kg exposure group. Overall, these findings suggest maternal propylparaben exposure may selectively impact estrous cyclicity and fertility outcomes in female offspring.