Prenatal exposure to bisphenol a at environmentally relevant doses adversely affects the murine female reproductive tract later in life.
BACKGROUND
Exposure to endocrine-disrupting chemicals during critical developmental periods causes adverse consequences later in life; an example is prenatal exposure to the pharmaceutical diethylstilbestrol (DES). Bisphenol A (BPA), an environmental estrogen used in the synthesis of plastics, is of concern because its chemical structure resembles that of DES, and it is a "high-volume production" chemical with widespread human exposure.


OBJECTIVE
In this study we investigated whether prenatal BPA causes long-term adverse effects in female reproductive tissues in an experimental animal model previously shown useful in studying effects of prenatal DES.


METHODS
Timed pregnant CD-1 mice were treated on days 9-16 of gestation with BPA (0.1, 1, 10, 100, or 1,000 mug/kg/day). After delivery, pups were held for 18 months; reproductive tissues were then evaluated.


RESULTS
Ovarian cysts were significantly increased in the 1-mug/kg BPA group; ovarian cyst-adenomas were seen in the other three BPA-treated groups but not in corn-oil controls. We observed increased progressive proliferative lesions of the oviduct after BPA treatment, similar to those described in response to DES. Further, although not statistically different from the controls, prominent mesonephric (Wolffian) remnants and squamous metaplasia of the uterus, as well as vaginal adenosis, were present in BPA-treated mice, similar to lesions reported following DES treatment. More severe pathologies observed in some BPA-treated animals included atypical hyperplasia and stromal polyps of the uterus; sarcoma of the uterine cervix; and mammary adenocarcinoma. We did not observe these lesions in controls.


CONCLUSIONS
These data suggest that BPA causes long-term adverse reproductive and carcinogenic effects if exposure occurs during critical periods of differentiation.
Newbold
Retha R
RR
Laboratory of Molecular Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina 27709, USA. newbold1@niehs.nih.gov
Jefferson
Wendy N
WN
Padilla-Banks
Elizabeth
E
D000818:Animals; D001559:Benzhydryl Compounds; D004054:Diethylstilbestrol / Q000633:toxicity; D052244:Endocrine Disruptors / Q000633:toxicity; D005260:Female; D051379:Mice; D010053:Ovary / Q000187:drug effects; D010636:Phenols / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012098:Reproduction / Q000187:drug effects*; D014599:Uterus / Q000187:drug effects; D014874:Water Pollutants, Chemical / Q000633:toxicity*; D000098826:Bisphenol A Compounds
D001559:Benzhydryl Compounds; D004054:Diethylstilbestrol; D052244:Endocrine Disruptors; D010636:Phenols; D014874:Water Pollutants, Chemical; C006780:bisphenol A; D000098826:Bisphenol A Compounds