目的:研究围生期双酚A(Bisphenol A,BPA)暴露对SD大鼠子代生殖系统的影响及雌激素受体(Estrogen Receptor,ER)表达的改变。方法:经灌胃给予围生期孕鼠0、5、50、500mg/(kg.d)的BPA,观察雌性子代生殖器官重量、病理学改变、子宫ERα、β及磷酸化ERK(p-ERK)与总ERK(T-ERK)蛋白表达的改变,并通过子宫增重实验检测子宫对雌二醇(E2)敏感性的改变。结果:500mg/kg BPA可引发亲代中毒症状及子代体重下降(P〈0.05),50mg/kg BPA可明显增加雌性子代体重及子宫重量,BPA各剂量组均可使子宫内膜增厚及相对比例增加,子宫增重和子宫相对增殖率增加,并提高ERα与p-ERK蛋白表达,而对ERβ无影响。结论:BPA围生期暴露可引起子代子宫组织ER蛋白表达变化,并可提高子宫对E2的敏感性。
OBJECTIVE:To explore the effect of perinatal exposure to bisophenol A(BPA)on reproduction and development of the female offspring of SD rats and the changes of uterine estrogen receptor(ER)expression.METHODS:Pregnant Sprague-Dawley rats received by gavage 0,5,50 or 500 mg/(kg·d)of BPA from gestation day(PND)6 to postnatal day(PND)21.Uterus and ovarians were weighed and prepared for histological evaluation.The expression of ERα,ERβ,phosphorylated ERK(p-ERK)and total ERK(T-ERK)in uterus were measured.The change of uterine sensitivity to estradiol(E2)was investigated by the modified uterotrophic assay.RESULTS:The toxic symptoms in parental rats and decrease in body weight in female offsprings were observed in 500 mg/(kg·BW)group,but there was an increase in body weight and uterine weight in the 50 mg/(kg·BW)group.No pathological changes were found in BPA-treated group,the thickness of endometrial layer and the ratio to uterus was increased in all dosage groups compared with the control.The protein expressions of ERα and p-ERK but not ERβ in uterus were elevated in all dosage groups.The uterine sensitivity to E2 was increased in all BPA-treated groups.CONCLUSION:Perinatal exposure to Bisphenol A could induce the changes of ER expression in the uterus of female offspring rats and change the uterine physical structure by probably activating the ERK pathway.