全氟辛烷磺酸盐对大鼠胚胎发育及胎盘IGF-1表达的影响

Effects of exposure to perfluorooctane sulphonate at different doses on embryonic development and expression of placental IGF-1 in rats

目的探讨不同剂量全氟辛烷磺酸盐(perfluorooctane sulphonate,PFOS)染毒对大鼠胚胎发育及胎盘胰岛素样生长因子-1(insulin-like growth factor 1,IGF-1)表达的影响。方法将孕12 d的48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),连续灌胃7 d,在孕19 d时处死孕鼠,检测孕鼠和胎鼠的体质量、胎鼠肝系数、孕鼠血清PFOS和糖皮质激素(glucocorticoid,GC)水平、胎盘IGF-1表达水平。结果与对照组相比,随着PFOS剂量增加,染毒组孕鼠血清PFOS显著蓄积,孕鼠体质量、胎鼠体质量和体长、胎盘质量均逐渐下降,PFOS 20 mg/kg组差异有显著性(P<0. 001);胎鼠肝系数也表现相同趋势,低中高剂量染毒组均显著低于对照组(P<0. 05),血液生化丙氨酸氨基转移酶(alanine aminotransferase,ALT)与天门冬氨酸氨基转移酶(aspartate aminotransferase,AST)也随着PFOS给药剂量的增加而增高(P<0. 05); PFOS 10 mg/kg组,孕鼠血清GC水平升高(P<0. 05);胎盘IGF-1表达水平随PFOS剂量升高而降低。结论孕期长期暴露PFOS会导致孕鼠血清PFOS含量蓄积,进而导致胎鼠肝毒性,GC含量升高,胎盘IGF-1表达水平降低,最终影响胎鼠的生长发育。

Objective To explore the effects of exposure to perfluorooctane sulphonate(PFOS)at different doses on embryonic development and expression of placental insulin-like growth factor 1(IGF-1)in rats.Methods At gestational day 12,pregnant rats were exposed to different doses of PFOS(0,5,10,and 20 mg/kg)by gavage for 7 d.At gestational day 19,the body masses of pregnant and fetal rats,liver organ coefficient of fetal rats,serum PFOS and glucocorticoid(GC)levels of pregnant rats,and IGF-1 mRNA level of placenta were measured.Results Compared with those in the control group,the serum PFOS levels of pregnant rats in the treatment groups were significantly higher with increasing PFOS dose,while the body mass of pregnant rats and the body mass and length of fetal rats exposed to 20 mg/kg PFOS were significantly lower(P<0.001).Fetal rat liver organ coefficient in the treatment group showed the same trend of a marked decrease(P<0.05).Blood biochemical alanine aminotransferase(ALT)and aspartate aminotransferase(AST)also increased with the dose of PFOS(P<0.05).Treatment with 10 mg/kg PFOS increased the serum GC level of pregnant rats(P<0.05).IGF-1 mRNA level decreased with the increasing PFOS dose in placenta.Conclusions PFOS exposure during pregnancy can lead to liver toxicity in fetal rats through the maternal accumulation of PFOS in the serum,increased GC concentration,and decreased IGF-1 mRNA expression,thereby affecting the growth and development of offsprings.