Abbott Barbara D, Wolf Cynthia J, Das Kaberi P, Zehr Robert D, Schmid Judith E, Lindstrom Andrew B, Strynar Mark J, Lau Christopher
Reproductive Toxicology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, NC 27711, United States.
Reproductive Toxicology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, NC 27711, United States.
Reprod Toxicol. 2009 Jun;27(3-4):258-265. doi: 10.1016/j.reprotox.2008.05.061. Epub 2008 May 24.
Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) are members of a family of perfluorinated compounds. Both are environmentally persistent and found in the serum of wildlife and humans. PFOS and PFOA are developmentally toxic in laboratory rodents. Exposure to these chemicals in utero delays development and reduces postnatal survival and growth. Exposure to PFOS on the last 4 days of gestation in the rat is sufficient to reduce neonatal survival. PFOS and PFOA are weak agonists of peroxisome proliferator activated receptor-alpha (PPAR alpha). The reduced postnatal survival of neonatal mice exposed to PFOA was recently shown to depend on expression of PPAR alpha. This study used PPAR alpha knockout (KO) and 129S1/SvlmJ wild type (WT) mice to determine if PPAR alpha expression is required for the developmental toxicity of PFOS. After mating overnight, the next day was designated gestation day (GD) 0. WT females were weighed and dosed orally from GD15 to 18 with 0.5% Tween-20, 4.5, 6.5, 8.5, or 10.5mg PFOS/kg/day. KO females were dosed with 0.5% Tween-20, 8.5 or 10.5mg PFOS/kg/day. Dams and pups were observed daily and pups were weighed on postnatal day (PND) 1 and PND15. Eye opening was recorded from PND12 to 15. Dams and pups were killed on PND15, body and liver weights recorded, and serum collected. PFOS did not affect maternal weight gain or body or liver weights of the dams on PND15. Neonatal survival (PND1-15) was significantly reduced by PFOS in both WT and KO litters at all doses. WT and KO pup birth weight and weight gain from PND1 to 15 were not significantly affected by PFOS exposure. Relative liver weight of WT and KO pups was significantly increased by the 10.5mg/kg dose. Eye opening of PFOS-exposed pups was slightly delayed in WT and KO on PND13 or 14, respectively. Because results in WT and KO were comparable, it is concluded that PFOS-induced neonatal lethality and delayed eye opening are not dependent on activation of PPAR alpha.
全氟辛烷磺酸（PFOS）和全氟辛酸（PFOA）是全氟化合物家族的成员。二者在环境中具有持久性，并且在野生动物和人类的血清中都能检测到。PFOS和PFOA对实验啮齿动物具有发育毒性。子宫内接触这些化学物质会延迟发育，并降低出生后的存活率和生长速度。在大鼠妊娠的最后4天接触PFOS就足以降低新生鼠的存活率。PFOS和PFOA是过氧化物酶体增殖物激活受体α（PPARα）的弱激动剂。最近研究表明，接触PFOA的新生小鼠出生后存活率降低取决于PPARα的表达。本研究使用PPARα基因敲除（KO）小鼠和129S1/SvlmJ野生型（WT）小鼠，以确定PFOS的发育毒性是否需要PPARα的表达。过夜交配后，次日定为妊娠第0天（GD0）。对WT雌性小鼠从妊娠第15天至18天每天经口灌胃给予0.5%吐温-20、4.5、6.5,、8.5或10.5mg PFOS/kg体重。对KO雌性小鼠每天经口灌胃给予0.5%吐温-20、8.5或10.5mg PFOS/kg体重。每天观察母鼠和幼鼠情况，并在出生后第1天（PND1）和第15天（PND15）对幼鼠称重。记录PND12至15天幼鼠睁眼情况。在PND15处死母鼠和幼鼠，记录体重和肝脏重量，并采集血清。PFOS对母鼠体重增加以及PND15时母鼠的体重和肝脏重量均无影响。所有剂量的PFOS均使WT和KO幼鼠窝的新生鼠存活率（PND1 - 15）显著降低。PFOS暴露对WT和KO幼鼠的出生体重以及PND1至15天的体重增加均无显著影响。10.5mg/kg剂量使WT和KO幼鼠的相对肝脏重量显著增加。PFOS暴露的幼鼠在PND13或14时，WT和KO幼鼠的睁眼分别稍有延迟。由于WT和KO的结果具有可比性，因此得出结论：PFOS诱导的新生鼠致死率和睁眼延迟不依赖于PPARα的激活。
