Maternal exposure to fenarimol promotes reproductive performance in mouse offspring

Although fenarimol is a widely used chlorinated fungicide applied to fruits and vegetables and is a suspected endocrine disrupter, transgenerational studies of low doses of fenarimol exposure are not currently available. The aims of this study are to address the effect of maternal exposure to low doses of fenarimol on the reproductive performance of offspring and to investigate the expression changes of genes associated with this effect. Pregnant mice were orally exposed to low doses (0, 2, 20, and 200 μg/kg body weight) of fenarimol during gestational and lactational periods, and their offspring were assessed. The body and organ weights and anogenital distance (AGD) of mice offspring (F1) maternally exposed to fenarimol were determined, and the reproductive performances of these mice were assessed by mating and ovarian follicular and sperm analyses. Fenarimol-exposed F1 mice had shortened AGDs, increased body weight with altered organ weights, increased number of pups, increased number of ovarian follicles, and enhanced sperm quality. Microarray data showed 82 upregulated and 743 downregulated genes in the ovaries of fenarimol-exposed mice, in which Cyp17a1, Cyp19a1, and ERβ were upregulated. In addition, Nobox, a pivotal gene required for proper folliculogenesis, was significantly increased in the ovaries of F1 mice. In conclusion, maternal exposure to fenarimol promotes normal reproductive function in female mouse offspring by increasing the expression levels of genes crucial for ovarian folliculogenesis, identifying fenarimol as a chemical that stimulates reproductive performance. Thus, consumption of fenarimol-contaminated diets by mothers may possibly alter normal reproductive function of offspring in humans and wildlife.