孕鼠PFOS暴露对糖皮质激素水平及胎鼠生长发育的影响

Effect of PFOS Exposure on the Glucocorticoid Concentration in Pregnant Rats and Fetal Rats Growth and Development

为探究孕期全氟辛烷磺酸(PFOS)暴露与母源糖皮质激素(GC)水平、胎鼠生长发育之间的关系,将孕期为12 d(GD12)的24只SD雌性大鼠,随机分为4组给予不同剂量的PFOS(0,5,10,20 mg·kg-1),连续灌胃7 d,在GD19时对孕鼠和胎鼠的体重、胎鼠肝脏系数和肝脏生化指标、孕鼠血清的生化指标和GC水平、胎盘11β-羟基类固醇脱氢酶2(11β-HSD2)的酶学活性和胰岛素样生长因子-1(IGF-1)的mRNA表达水平分别进行检测。结果表明,与对照组相比:PFOS 20 mg·kg-1组,母鼠体重、胎鼠体重和体长显著下降(P<0.001);PFOS 20 mg·kg-1组,胎鼠肝脏脏器系数低于对照组(P<0.001);PFOS 10 mg·kg-1组,胎鼠肝脏中的酶活性(ALT、AST和ALP等)显著升高(P<0.001);PFOS 20 mg·kg-1组,孕鼠血清GC水平升高(P<0.05);胎盘IGF-1的mRNA表达水平随PFOS剂量升高而降低;胎盘11β-HSD2的活性随PFOS剂量升高而降低。研究表明,孕期暴露PFOS可以导致胎鼠肝脏毒性,降低胎盘11β-HSD2氧化活性导致GC浓度升高,进而影响胎鼠的生长发育。

To explore the effect of PFOS exposure on the maternal glucocorticoid levels and fetal growth and de- velopment, the GD12 pregnancy rats were exposed to different doses of PFOS （0, 5, 10 and 20 mg·kg^-1） by gavage for 7 d. At GD19, the body weight of pregnancy and fetal rats, liver biochemical index and liver organ coefficient of fetal rats, serum biochemical index and GC of pregnancy rats, 11β-HSD2 activity and IGF-1 mRNA level of placenta were measured. The results showed that the body weight of pregnancy rats and the body weight and length of fetal rats exposed to 20 mg.kg~ of PFOS were significantly lower than the control group （P〈0.001）; fetal rats liver organ coefficient of 20 mg.kg~ PFOS group markedly decreased （P〈0.001）; 10 mg-kg~ PFOS treatment in- creased fetal rats liver enzyme activities （ALT, AST, and ALP） （P〈0.001）; pregnant rat serum glucocorticoids level in 20 mg-kg~ group increased （P〈0.05）; IGF-1 mRNA level decreased with PFOS dose increasing in placenta; 1113-HSD2 activity decreased with PFOS increasing in placenta. This study showed that exposure to PFOS during pregnancy can lead to fetal rats liver toxicity, reduce placental 11β-HSD2 oxidative activity, increase GC concentra- tion, thereby affect the growth and development of offspring.