Prenatal exposure to bisphenol A analogues on female reproductive functions in mice.
Toxicol Sci. 2019 Jan 10. Epub 2019 Jan 10. PMID: 30629253
This study was performed to examine whether prenatal exposure to bisphenol (BP) A analogues, BPE and BPS, negatively impacts female reproductive functions and follicular development using mice as a model. CD-1 mice were orally exposed to control treatment (corn oil), BPA, BPE or BPS (0.5, 20 or 50µg/kg/day) from gestational day 11 (the presence of vaginal plug = 1) to birth. Exposure to BPA, BPE and BPS accelerated the onset of puberty and exhibited abnormal estrous cyclicity, especially with lower doses. Females exposed to BPA, BPE and BPS exhibited mating difficulties starting at 6 monthsof age. By 9 months, mice exhibited various fertility problems including reduced pregnancy rate, parturition issues, and increased dead pups at birth. Furthermore, the levels of serum testosterone were elevated by BPE or BPS exposure at the age of 9 months, whereas estrogen levels were not affected. On the other hand, the dysregulated expression of steroidogenic enzymes was observed in the ovary at 3, 6 or 9 months of age by BPE or BPS exposure. When we examined neonatal ovary on postnatal day 4, BPA, BPE and BPS exposure inhibited germ cell nest breakdown and reduced numbers of primary and secondary follicles. These results suggest that prenatal exposure to BPA analogues, BPE and BPS, have effects on fertility in later reproductive life probably due to the disruption of early folliculogenesis.