ToxSci Advance Access published online on October 28, 2009
Toxicological Sciences, doi:10.1093/toxsci/kfp266
Published by Oxford University Press 2009.
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
,*,**,*
Reproductive Toxicology Branch, TA Division, NHEERL, ORD, USEPA
* Department of Molecular Biosciences, North Carolina State University/US EPA Cooperative Training Program
** Department of Zoology, North Carolina State University
IS Division, NHEERL, ORD, USEPA
Send correspondence to; L Earl Gray Jr, MD 72, 2525 Highway 54, RTP, NC, 27711, Email: emgray{at}mindspring.com
Received September 14, 2009; revision received October 14, 2009; accepted October 15, 2009
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Abstract |
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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 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 LE rat offspring.
Pregnant rats were gavaged with vehicle, EE2 (0.05 to 50 µg/kg/day) or BPA (2, 20 and 200 µg/kg/day) from day 7 of gestation to postnatal day 18 and the female offspring were studied. EE2 (50 µg/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 µg/kg). F1 females exposed to EE2 also displayed a reduced (male-like) saccharin preference (5 µg/kg) and absence of lordosis behavior (15 µg/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.
Key Words: ethinyl estradiol; bisphenol A; rat; reproductive toxicology; sexually dimorphic behavior.
DISCLAIMER: The research described in this article has been reviewed by the National Health and Environmental Effects Research Laboratory, ORD, U. S. Environmental Protection Agency, and approved for publication. Approval does not signify that the contents necessarily reflect the views and policies of the Agency nor does the mention of trade names or commercial products constitute endorsement or recommendation for use.