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Testing the Uterotrophic Activity of Perfluorooctanoic Acid (PFOA) in the Immature CD-1 Mouse
Citation:
HINES, E P., E A. GIBBS-FLOURNOY, J STANKO, R. NEWBOLD, W. JEFFERSON, AND S E. FENTON. Testing the Uterotrophic Activity of Perfluorooctanoic Acid (PFOA) in the Immature CD-1 Mouse. Presented at 2009 SOT Annual Meeting, Baltimore, MD, March 15 - 19, 2009.
Impact/Purpose:
To present at the 2009 SOT Annual Meeting
Description:
The uterotrophic assay is an in vivo screening tool used to determine the estrogenic or anti-estrogenic potential of an exogenously administered compound. Recent studies reported that PFOA increased activity of estrogen-responsive genes in fish, some in association with liver tumors. Thus, we explored the effect of PFOA on the immature mouse uterus using a standardized uterotrophic assay. Timed-pregnant CD-1 dams (N=17) delivered litters that were equalized to 10 female pups within 18 hr of birth. Early on postnatal day (PND) 18, pups were weaned, weighed, and assigned to treatment groups of equal weight. That same day, pups were treated by oral gavage with PFOA (0, 0.01, 0.1, or 1 mg PFOA/kg body weight (BW)) with or without 17-β estradiol in corn oil (E2, 500 μg/kg, s.c.). All mice not receiving E2 received a corn oil vehicle s.c. injection. The mice (N=16/non-E2 group, N=8/E2 group) were weighed and dosed for 3 consecutive days and killed on PND 21. BW and uterine wet weights (UWW) were recorded, and uteri were fixed in buffered formalin for future histopathology. BW was unchanged by PFOA treatment. There was a significant increase in the UWW and UWW:BW ratio (% BW) at 0.01 mg PFOA/kg (p<0.05) that is most likely due to enlargement of the uterine cervix junction, visibly enlarged in >75% of the PFOA-animals regardless of E2 status. UWW and % BW ratios for 0, 0.01, 0.1, and 1 mg/kg PFOA were 13+1, 20+1, 16+2, and 16+2 mg, and 0.11+0.01, 0.16+0.01, 0.14+0.01, and 0.13+0.01, respectively. E2 induced a significant increase in UWW in all groups (mean % BW 0.86+0.06). No anti-estrogenic effects were found by co-administration of PFOA with E2. PFOA produced a unique effect at the utero-cervical junction that was distinct from the uterine effect of estrogen. Histological analysis will be required to determine the specific cell types affected by PFOA exposure. These data do not necessarily reflect EPA policy.