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Developmental Effects of Perfluorononanoic acid in the Mouse Are Dependent on Peroxisome Proliferator-Activated Receptor-alpha
Citation:
WOLF, C. J., R. ZEHR, J. E. SCHMID, C. LAU, AND B. D. ABBOTT. Developmental Effects of Perfluorononanoic acid in the Mouse Are Dependent on Peroxisome Proliferator-Activated Receptor-alpha. PPAR research. Hindawi Publishing Corporation, New York, NY, 1(pii):282896, (2010).
Impact/Purpose:
Prenatal exposure to PFNA negatively impacts survival and development of mice and activates the mouse and human peroxisome proliferator-activated receptor-alpha (PPARa).
Description:
Perfluorononanoic acid (PFNA) is one ofthe perfluoroalkyl acids found in the environment and in tissues of humans and wildlife. Prenatal exposure to PFNA negatively impacts survival and development of mice and activates the mouse and human peroxisome proliferator-activated receptor-alpha (PPARa). In the current study, we used PPARa-knockout (KO) and 129Sl/SvlmJ wild type (WT) mice to investigate the role ofPPARa in mediating PFNA-induced in vivo effects. Pregnant KO and WT mice were dosed orally with water (vehicle control; 10 ml/kg), 0.83, 1.1, 1.5, or 2 mg/kg PFNA on gestational days (OD) 1-18 (day of sperm plug = OD 0). Maternal weight gain, implantation, litter size, and pup weight at birth were unaffected in either strain. PFNA exposure reduced the number of live pups at birth and survival of offspring to weaning in the 1.1 and 2 mg/kg groups in WT. Eye opening was delayed (mean delay = 2.1 days) and pup weight at weaning was reduced in WT pups at 2 mg/kg. These developmental endpoints were not affected in the KO. Relative liver weight was increased in a dose-dependent manner in dams and pups of the WT strain at all dose levels, but only slightly increased in the highest dose group in the KO strain. In summary, PFNA altered liver weight of dams and pups, and pup survival, body weight, and development in the WT, while only inducing a slight increase in relative liver weight of dams and pups at 2 mg/kg in KO mice. These results suggest that PPARa is an essential mediator of PFNA-induced developmental toxicity in the mouse.
