癌变·畸变·突变 ›› 2010, Vol. 22 ›› Issue (3): 196-201.doi: 10.3969/j.issn.1004-616x.2010.03.009

• 论著 • 上一篇    下一篇

围生期双酚A暴露对大鼠雌性子代生殖系统及雌激素受体表达的影响

陈以偿;郝卫东;尚兰琴;魏雪涛;蒋建军;刘然;邢丽娜;吴双   

  1. 北京大学公共卫生学院毒理学系,北京 100191
  • 收稿日期:2010-03-05 修回日期:2010-03-20 出版日期:2010-05-30 发布日期:2010-05-30
  • 通讯作者: 郝卫东

The effect of perinatal exposure to Bisophenol A on reproductive system of female offspring rats and changes in expression of estrogen receptor

CHEN Yin-chang;HAO Wei-dong;SHANG Lan-qin;WEI Xue-tao;JIANG Jian-jun;LIU Ran;XING Li-na;WU Shuang   

  1. Department of Toxicology, School of Public Health, Peking University, Beijing 100191, China
  • Received:2010-03-05 Revised:2010-03-20 Online:2010-05-30 Published:2010-05-30
  • Contact: HAO Wei-dong

摘要: 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、500 mg/(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: 500 mg/kg BPA可引发亲代中毒症状及子代体重下降(P<0.05),50 mg/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。

关键词: 双酚A, 雌性仔鼠, 生殖和发育, 雌激素受体, 细胞外调节蛋白激酶

Abstract: 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.

Key words: Bisphenol A, female offspring, reproductive and developmental effects, estrogen receptor, extracellular regulated kinase

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