ToxSci Advance Access originally published online on November 28, 2006
Toxicological Sciences 2007 96(1):133-144; doi:10.1093/toxsci/kfl177
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Published by Oxford University Press 2006.
Gestational PFOA Exposure of Mice is Associated with Altered Mammary Gland Development in Dams and Female Offspring
,
,1,2
* Curriculum in Toxicology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599
Reproductive Toxicology Division, ORD/National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency, Research Triangle Park, North Carolina 27711
Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, Georgia 30341
Department of Chemistry, North Carolina Central University, Durham, North Carolina 27709
¶ Human Exposure and Atmospheric Sciences Division, ORD/National Exposure Research Laboratory, US Environmental Protection Agency, Research Triangle Park, North Carolina 27711
2 To whom correspondence should be addressed at Reproductive Toxicology Division, ORD/National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency, MD-67, 2525 East Highway 54, Research Triangle Park, NC 27711. Fax: (919) 541-4017. Email: fenton.suzanne{at}epa.gov.
Received August 31, 2006; accepted November 21, 2006
 |
Abstract |
|---|
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 (BWs) 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 vehicle on GD 1–17. PFOA exposure had no effect on maternal weight gain or number of live pups born. Mean pup BWs on postnatal day (PND) 1 in all PFOA-exposed groups were significantly reduced and decrements persisted until weaning. Mammary glands from lactating dams and female pups on PND 10 and 20 were scored based on differentiation or developmental stages. A significant reduction in mammary differentiation among dams exposed GD 1–17 or 8–17 was evident on PND 10. On PND 20, 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 PND 10 and 20. While control litters at PND 10 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. BW 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.
Key Words: mammary gland; PFOA; lactation; development; pregnancy.
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 Centers for Disease Control. 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.
1 Present address: UNC-Chapel Hill, School of Medicine, Chapel Hill, NC 27599.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  M. B. Rosen, C. Lau, and J. C. Corton Does Exposure to Perfluoroalkyl Acids Present a Risk to Human Health? Toxicol. Sci., September 1, 2009; 111(1): 1 - 3. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Lou, J. F. Wambaugh, C. Lau, R. G. Hanson, A. B. Lindstrom, M. J. Strynar, R. D. Zehr, R. W. Setzer, and H. A. Barton Modeling Single and Repeated Dose Pharmacokinetics of PFOA in Mice Toxicol. Sci., February 1, 2009; 107(2): 331 - 341. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. J. Wolf, M. L. Takacs, J. E. Schmid, C. Lau, and B. D. Abbott Activation of Mouse and Human Peroxisome Proliferator-Activated Receptor Alpha by Perfluoroalkyl Acids of Different Functional Groups and Chain Lengths Toxicol. Sci., November 1, 2008; 106(1): 162 - 171. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. P. Das, B. E. Grey, R. D. Zehr, C. R. Wood, J. L. Butenhoff, S.-C. Chang, D. J. Ehresman, Y.-M. Tan, and C. Lau Effects of Perfluorobutyrate Exposure during Pregnancy in the Mouse Toxicol. Sci., September 1, 2008; 105(1): 173 - 181. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Lau, K. Anitole, C. Hodes, D. Lai, A. Pfahles-Hutchens, and J. Seed Perfluoroalkyl Acids: A Review of Monitoring and Toxicological Findings Toxicol. Sci., October 1, 2007; 99(2): 366 - 394. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Fuentes, M. T. Colomina, P. Vicens, N. Franco-Pons, and J. L. Domingo Concurrent Exposure to Perfluorooctane Sulfonate and Restraint Stress during Pregnancy in Mice: Effects on Postnatal Development and Behavior of the Offspring Toxicol. Sci., August 1, 2007; 98(2): 589 - 598. [Abstract] [Full Text] [PDF]
|
|