ToxSci Advance Access published online on November 28, 2006
Toxicological Sciences, doi:10.1093/toxsci/kfl177
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1 Curriculum in Toxicology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599; Reproductive Toxicology Division, ORD/National Health and Environmental Effects Research Laboratory
* To whom correspondence should be addressed. Perfluorooctanoic acid (PFOA), with diverse and widespread commercial and industrial applications, has been detected in human and wildlife sera. Previous mouse studies linked prenatal PFOA exposure to decreased neonatal body weights and survival in a dose-dependent manner. To determine whether effects were linked to gestational time of exposure or to subsequent lactational changes, timed pregnant CD-1 mice were orally dosed with 5 mg PFOA/kg on gestation days (GD) 1-17, 8-17, 12-17, or to vehicle on GD1-17. PFOA exposure had no effect on maternal weight gain or number of live pups born. Mean pup body weights on postnatal day (PND) 1 in all PFOA-exposed groups were significantly reduced and decrements remained until weaning. Mammary glands from lactating dams and female pups on PND10 and 20 were scored based on differentiation or developmental stages. A significant reduction in mammary differentiation among dams exposed GD1-17 or 8-17 was evident on PND10. On PND20, delays in normal epithelial involution and alterations in milk protein gene expression were observed. All exposed female pups displayed stunted mammary epithelial branching and growth at PND10 and 20. While control litters at PND10 and 20 had average scores of 3.1 and 3.3 respectively, all treated litters had scores of 1.7 or less, with no progression of duct epithelial growth evident over time. Body weight was an insignificant covariate for these effects. These findings suggest that in addition to gestational exposure, abnormal lactational development of dams may play a role in early growth retardation of developmentally exposed offspring. Disclaimer: The information in this document has been funded by the U.S. Environmental Protection Agency. It has been subjected to review by the National Health and Environmental Effects Research Laboratory and approved for publication. Approval does not signify that the contents reflect the views of the Agency, nor does mention of trade names or commercial products constitute endorsement or recommendation for use. Furthermore, the findings and conclusions in this report are those of the authors and do not necessarily represent the views of the CDC. Portions of these data within this manuscript were presented at the Society of Toxicology Meeting in San Diego, CA, March 2006 and the Society for the Study of Reproduction Meeting in Quebec, Canada, July 2005.
Received August 31, 2006
Accepted November 21, 2006
Reproductive and Developmental Toxicology
Gestational PFOA Exposure of Mice is Associated with Altered Mammary Gland Development in Dams and Female Offspring
Sally S. White 1, Antonia M.Calafat 2, Zsuzsanna Kuklenyik 2, LaTonya Villanueva 3, Robert D. Zehr 4, Laurence Helfant 5, Mark J. Strynar 5, Andrew B. Lindstrom 5, Julie R. Thibodeaux 6, Carmen Wood 4, and Suzanne E. Fenton 4 *
2 Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA 30341
3 Reproductive Toxicology Division, ORD/National Health and Environmental Effects Research Laboratory; Department of Chemistry, North Carolina Central University, Durham, NC 27709
4 Reproductive Toxicology Division, ORD/National Health and Environmental Effects Research Laboratory
5 Human Exposure and Atmospheric Sciences Division, ORD/National Exposure Research Laboratory, US Environmental Protection Agency, Research Triangle Park, NC 27711
6 Reproductive Toxicology Division, ORD/National Health and Environmental Effects Research Laboratory; Present Address: UNC-Chapel Hill, School of Medicine, Chapel Hill, NC, 27599
Suzanne E. Fenton, E-mail: fenton.suzanne{at}epa.gov
Abstract
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