妊娠期全氟辛酸染毒对子代雄鼠发育毒性的研究

Effect of pregnancy exposure to perfluorooctanoic acid(PFOA) on the developmental toxicity of male offspring mice

探讨妊娠期染毒全氟辛酸(perfluorooctanoic acid,PFOA)对子代雄鼠发育毒性的影响.将50只妊娠0 d小鼠随机分5组,每组10只,妊娠0~17 d每天按0、1、2.5、5和12.5 mg·kg^(-1)BW饲喂PFOA,产后仔鼠正常饲养,记录仔鼠存活数.产后21 d,检测仔鼠血清睾酮水平并计算睾丸指数;HE染色观察睾丸组织结构变化;RT-PCR法检测睾丸组织Dlk1-Dio3印记基因簇各目的基因mRNA的表达情况.结果显示,随PFOA染毒剂量增加,仔鼠存活数显著降低,血清睾酮含量极显著性降低(p<0.01);睾丸指数无统计学意义;睾丸组织有不同程度的损伤并呈剂量依赖性;Dlk1-Dio3印记基因簇各目的基因的表达量都有降低趋势,其中Gtl2、Rian、Dio3均显著性降低(p<0.05).结果表明,妊娠期染毒PFOA能够降低仔鼠存活数,损伤睾丸组织结构,并能够扰乱生殖激素,降低睾丸组织Dlk1-Dio3印记基因簇各目的基因mRNA的表达.

To explore the effects of pregnancy exposure to Perfluorooctanoic Acid（ PFOA） on the developmental toxicity of male offspring mice,fifty pregnant mice were randomly divided into 5 groups with 10 of each,which were fed with 0,1,2.5,5 and 12.5 mg·kg^-1BW of PFOA contaminated feed,respectively,from the pregnancy day 0 to day 17. The offspring mice were fed with normal diets after delivery and the survival number was recorded. The testis coefficient and serum testosterone concentration was checked at postpartum day 21 and the testicular histomorphology were observed with hematoxylin-eosin staining（ HE）. The expression of mRNA of target gene in Dlk1-Dio3 imprinting gene cluster in testicular tissue were measured using RT-PCR. Results showed that with the dose of PFOA increasing,both the survival number of offspring mice and the serum testosterone levels were significantly decreased（ p〈0.01）,while there was no significant statistical difference in the testis coefficient among the groups. HE staining showed the testicular damages in a dose-dependent manner. The expression of target genes of Dlk1-Dio3 imprinting gene cluster had a decreasing trend with increasing PFOA dosage,within which Gtl2,Rian and Dio3 gene were significantly lowered（ p〈0.05）. The results indicated that PFOA exposing during pregnancy could reduce the survival number of offspring mice,damage the testicular tissue structure,disrupt reproductive hormones and reduce the expression level of mRNA of target genes of Dlk1-Dio3 imprinting gene cluster of testicular tissue.