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PRENATAL EXPOSURE TO LOW DOSE PFOA INDUCES LOW DEVELOPMENTAL BODY WEIGHT FOLLOWED BY ADULT ONSET OBESITY THAT IS BLUNTED IN OVARIECTOMIZED ANIMALS
Citation:
HINES, E. P., S. WHITE, J. STANKO, AND S. E. FENTON. PRENATAL EXPOSURE TO LOW DOSE PFOA INDUCES LOW DEVELOPMENTAL BODY WEIGHT FOLLOWED BY ADULT ONSET OBESITY THAT IS BLUNTED IN OVARIECTOMIZED ANIMALS. Presented at Society for the Study of Reproduction, San Antonio, TX, July 21 - 25, 2007.
Description:
The Barker hypothesis, or fetal origins of adult disease, proposes that individuals born to mothers who were pregnant during lean times develop a "thrifty" phenotype with a smaller body size and lowered metabolic rates, leading to a propensity for obesity and development of disorders like diabetes and heart disease as adults. PFOA, an environmentally persistent chemical detected in humans and wildlife, is a surfactant with wide consumer and industrial applications. Developmental exposure to PFOA is associated with decreased body weight in neonates as well as other later life effects. This study addresses whether prenatal exposure to PFOA also leads to adult disease such as obesity and glucose intolerance using timed pregnant CD-1 mice (2 blocks) that were exposed to PFOA (0.01, 0.1, 0.3, and 1 or 5 mg/kg/day) via oral gavage over days 1 to 17 of pregnancy. Treated dams gave birth to pups at term (day 18) that had decreased body weights versus control. To address the role of ovarian hormones in programming of weight gain, half of the pups in all treatment groups were ovariectomized (ovx) at PND 21 or 22. Animal weights recorded at 12, 24, and 48 weeks were analyzed for treatment or ovary-related effects. At 12 weeks, ovx controls were 6.8% heavier than control counterparts; treated animals (0.1-1 mg/kg) were not significantly different from controls. However, the 5mg/kg PFOA animals were 11% lighter than controls at 12 weeks. At 24 weeks, ovx controls were 16% heavier than intact controls and although there was no dose dependent change (0.01-1mg/kg PFOA), there was a 5.8-10.9% increased weight of PFOA treated animals as compared with controls over that dose range. The 5mg/kg intact animals weighed 9% less than intact controls, and the 5mg/kg ovx animals weighed 6.5% more than the intact 5mg/kg animals. At 48 weeks in intact PFOA-exposed animals, there was a dose-dependent significant increase in weight versus untreated controls with the increased weight ranging from 17% (0.01mg/kg) to 23.3% (1mg/kg). The 5mg/kg group was similar in weight to control mice. The ovx unexposed controls were 64% heavier than the intact controls, as expected. Further, at 48 weeks, the PFOA-treated and ovx animals within a dose ranged only 1-9% different in weight. However, the PFOA treated ovx animals gained significantly less weight than control ovx animals (20-29%). The body mass indicies were measured at 42 weeks using a Bruker Optics Body Mass Analyzer, which determines the amount of fat, lean and fluid in live animals. The lean to body fat ratio in controls was 1.6, whereas the 0.01 and 0.1 mg/kg PFOA animals had nominally more fat than control pups (1.29, 1.29, respectively). We also noted that animals in the 5mg/kg group (intact and ovx) had significantly less body fat (2.5, 2.2, respectively, p<0.001). Judging from these preliminary data in an ongoing study, developmental PFOA treatment, even at doses within 100x of human exposure led to significantly increased weight gain over time and we surprisingly saw decreased weight gain in PFOA-treated ovx animals vs. ovx controls. These data suggest that prenatal PFOA exposure causes biological changes affecting body weight gain over time that are independent of those ovarian effects modulating weight.