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GESTATIONAL PFOA EXPOSURE OF MICE IS ASSOCIATED WITH ALTERED MAMMARY GLAND DEVELOPMENT IN DAMS AND FEMALE OFFSPRING
Citation:
WHITE, S. S., J. RAYNER, E. P. HINES, J. R. THIBODEAUX, AND S. E. FENTON. GESTATIONAL PFOA EXPOSURE OF MICE IS ASSOCIATED WITH ALTERED MAMMARY GLAND DEVELOPMENT IN DAMS AND FEMALE OFFSPRING. Presented at Society of Toxicology, San Diego, CA, March 05 - 09, 2006.
Description:
Perfluorooctanoic acid (PFOA), a ubiquitous and persistent synthetic compound, has been detected in human serum. Previous studies in mice linked prenatal PFOA exposure to increased neonatal mortality and decreased pup weights, in a dose responsive manner. To determine whether developmental effects were linked to impaired lactation or developmental exposures, time pregnant CD-1 mice (N=8-13 dams/group) were exposed to 5 mg/kg PFOA on gestation days (GD) 2-18, 9-18, 13-18, or to vehicle GD2-18. None of the PFOA exposures affected maternal weight gain or the number of live pups born. Mean pup weights on postnatal day 1 (PND 1) were significantly reduced compared to controls (from 6-14%; p<0.05) by all PFOA exposures. Body weights of pups were reduced by PFOA on PND 5, 10, and 20, in a time-dependent manner (25-44%, 30-43%, 30-36% from controls, respectively, p<0.0008). Mammary glands (MG) were removed from lactating dams and female pups at necropsy on PND 10 and 20. MGs were scored for development on a 1-4 scale. A significant reduction in MG development of the dams exposed from GD2-18 or 9-18 was evident (p<0.01) on PND10 (peak of lactation). On PND20 (weaning), involution of control MG alveoli was noted, but a delay in this process was evident in exposed dams. All exposed female pups at PND10 or 20 displayed stunted MG epithelial branching and growth compared to controls (p<0.001). 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 growth evident over time. Body weight was an insignificant covariate for these effects. These findings suggest that abnormal MG development of dams may play a substantial role in the early weight gain deficits in gestationally exposed offspring. Prenatal PFOA exposures cause detrimental effects on dam and offspring MG development. (This abstract does not necessarily reflect EPA policy.)