Long-term adverse effects of neonatal exposure to bisphenol A on the murine female reproductive tract.
The developing fetus is uniquely sensitive to perturbation by chemicals with hormone-like activity. The adverse effects of prenatal diethylstilbestrol (DES) exposure are a classic example. Since concern has been mounting regarding the human health and environmental effects of bisphenol A (BPA), a high-production-volume chemical with estrogenic activity used in the synthesis of plastics, we investigated its long-term effects in an experimental animal model that was previously shown useful in studying the adverse effects of developmental exposure to DES. Outbred female CD-1 mice were treated on days 1-5 with subcutaneous injections of BPA (10, 100 or 1000 microg/kg/day) dissolved in corn oil or corn oil alone (Control). At 18 months, ovaries and reproductive tract tissues were examined. There was a statistically significant increase in cystic ovaries and cystic endometrial hyperplasia (CEH) in the BPA-100 group as compared to Controls. Progressive proliferative lesion (PPL) of the oviduct and cystic mesonephric (Wolffian) duct remnants were also seen in all of the BPA groups. More severe pathologies of the uterus following neonatal BPA treatment included adenomyosis, leiomyomas, atypical hyperplasia, and stromal polyps. These data suggest that BPA causes long-term adverse effects if exposure occurs during critical periods of differentiation.
Newbold
Retha R
RR
Developmental Endocrinology and Endocrine Disruptor Section, Laboratory of Molecular Toxicology, National Institute of Environmental Health Sciences, NIH, DHHS, Research Triangle Park, NC 27709, USA. newbold1@niehs.nih.gov
Jefferson
Wendy N
WN
Padilla-Banks
Elizabeth
E
D000230:Adenocarcinoma / Q000139:chemically induced / Q000473:pathology; D000818:Animals; D000831:Animals, Newborn; D021461:Animals, Outbred Strains; D001559:Benzhydryl Compounds; D001835:Body Weight / Q000187:drug effects; D003338:Corpus Luteum / Q000187:drug effects / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004714:Endometrial Hyperplasia / Q000139:chemically induced / Q000473:pathology; D004715:Endometriosis / Q000139:chemically induced / Q000473:pathology; D004968:Estrogens, Non-Steroidal / Q000008:administration & dosage / Q000633:toxicity; D005260:Female; D007279:Injections, Subcutaneous; D007889:Leiomyoma / Q000139:chemically induced / Q000473:pathology; D008297:Male; D051379:Mice; D010048:Ovarian Cysts / Q000139:chemically induced / Q000473:pathology; D010053:Ovary / Q000187:drug effects* / Q000473:pathology; D010057:Oviducts / Q000187:drug effects / Q000473:pathology; D010636:Phenols / Q000008:administration & dosage / Q000633:toxicity*; D011247:Pregnancy; D013997:Time Factors; D014594:Uterine Neoplasms / Q000139:chemically induced / Q000473:pathology; D014599:Uterus / Q000187:drug effects / Q000473:pathology; D000098826:Bisphenol A Compounds