PARENT SESSION

(T275) STUNTED MOUSE MAMMARY GLAND DEVELOPMENT, IN THE ABSENCE OF BODY WEIGHT EFFECTS, FOLLOWING PRENATAL EXPOSURE TO PFOA.

White, Sally¹, Rayner, Jennifer ¹, Hines, Erin², Thibodeaux, Julie², Fenton, Suzanne², ¹ University of North Carolina, Chapel Hill, NC² US EPA, Research Triangle Park, NC

ABSTRACT- Perfluorooctanoic acid (PFOA), a synthetic compound resistant to degradation, is ubiquitous in the environment and is detected in sera of humans and several wildlife species. Previous studies in mice have demonstrated that prenatal exposure to PFOA leads to increased postnatal mortality and decreased pup weights, in a dose responsive manner. This raises the question of whether these growth deficits would result in mammary gland growth effects. In the current study, time pregnant CD-1 mice (N=8-12 dams/dose group) were exposed to 5 mg/kg PFOA (a dosage previously shown to affect pup growth but not viability) from gestation days (GD) 2-18, 9-18, or 13-18. Controls received water. Our goal was to determine if there was an exposure window that was necessary to elicit decreased pup weight gain. There was no effect of exposure on live pups born per dam. Litter weights were similar between exposed and control groups at birth (postnatal day [PND] 1) and no effects on maternal weight gain during pregnancy were observed. However, by PND 5 there was a significant decrease in weight of the GD 2-18 litters compared to the other dose groups (reduced by 44% from controls, p<0.0001). The litters exposed GD 2-18 continued to be smaller than litters in all other groups on PND 10 and 20 (reduced by 43 and 48% vs. controls; p<0.001), whereas the other dose groups were decreased by a maximum of 12% compared to controls (p>0.05). Mammary glands were removed from female pups at necropsy on PND 10 and 20. Interestingly, all PFOA-exposed litters at both ages displayed stunted mammary epithelial branching and growth compared to controls (p<0.001). Glands were scored (by 2 scorers) for development on a 4 point scale. While control litters on PND 10 and 20 had average scores of 3.1 and 3.3, respectively, all treated litters had scores of 1.7 or less. In fact, there was abnormal lack of progression of mammary gland growth in treated litters over time. These findings lead us to believe that even brief prenatal exposures may lead to detrimental effects of PFOA on offspring mammary gland development in the absence of effects on their weight gain. Whether the pup body weight effects are mediated via the dams milk are under investigation.(This abstract does not necessarily reflect EPA policy.)

KEY WORDS: mammary gland, perfluorooctanoic acid, body weight, development