In utero and lactational exposure to bisphenol A, in contrast to ethinyl estradiol, does not alter sexually dimorphic behavior, puberty, fertility, and anatomy of female LE rats.
Many chemicals released into the environment display estrogenic activity including the oral contraceptive ethinyl estradiol (EE2) and the plastic monomer bisphenol A (BPA). EE2 is present in some aquatic systems at concentrations sufficient to alter reproductive function of fishes. Many concerns have been raised about the potential effects of BPA. The National Toxicology Program rated the potential effects of low doses of BPA on behavior and central nervous system (CNS) as an area of "some concern," whereas most effects were rated as of "negligible" or "minimal" concern. However, the number of robust studies in this area was limited. The current study was designed to determine if maternal exposure to relatively low oral doses of EE2 or BPA in utero and during lactation would alter the expression of well-characterized sexually dimorphic behaviors or alter the age of puberty or reproductive function in the female Long-Evans rat offspring. Pregnant rats were gavaged with vehicle, EE2 (0.05-50 microg/kg/day), or BPA (2, 20, and 200 microg/kg/day) from day 7 of gestation to postnatal day (PND) 18, and the female offspring were studied. EE2 (50 microg/kg/day) increased anogenital distance and reduced pup body weight at PND2, accelerated the age at vaginal opening, reduced F1 fertility and F2 litter sizes, and induced malformations of the external genitalia (5 microg/kg). F1 females exposed to EE2 also displayed a reduced (male-like) saccharin preference (5 microg/kg) and absence of lordosis behavior (15 microg/kg), indications of defeminization of the CNS. BPA had no effect on any of the aforementioned measures. These results demonstrate that developmental exposure to pharmacologically relevant dosage levels of EE2 can permanently disrupt the reproductive morphology and function of the female rat.
Reproductive Toxicology Branch, TA Division, National Health and Environmental Effects Research Laboratory, ORD, U.S. Environmental Protection Agency Office of Research and Development, Research Triangle Park, North Carolina 27711, USA.
Bryce C
BC
Ryan
Andrew K
AK
Hotchkiss
Kevin M
KM
Crofton
L Earl
LE
Gray
D000818:Animals; D001559:Benzhydryl Compounds; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000633:toxicity*; D004968:Estrogens, Non-Steroidal / Q000633:toxicity*; D004997:Ethinyl Estradiol / Q000633:toxicity; D005260:Female; D005298:Fertility / Q000187:drug effects*; D005836:Genitalia, Female / Q000002:abnormalities / Q000187:drug effects; D007774:Lactation; D008297:Male; D018811:Maternal Exposure; D009043:Motor Activity / Q000187:drug effects; D010636:Phenols / Q000633:toxicity*; D011247:Pregnancy; D051381:Rats; D020318:Rats, Long-Evans; D012727:Sex Characteristics; D012726:Sexual Behavior, Animal / Q000187:drug effects*; D012741:Sexual Maturation; D018675:Toxicity Tests; D000098826:Bisphenol A Compounds
D001559:Benzhydryl Compounds; D004785:Environmental Pollutants; D004968:Estrogens, Non-Steroidal; D004997:Ethinyl Estradiol; D010636:Phenols; C006780:bisphenol A; D000098826:Bisphenol A Compounds