围产期母体染毒双酚A对雄性子代脑内雌激素β受体和芳香酶表达的影响  

EFFECTS OF PERINATAL EXPOSURE TO BISPHENOL-A ON EXPRESSION OF ESTROGEN RECEPTOR-BETA AND P450AROM OF THE BRAIN IN MALE OFFSPRING RAT

作　　者：王亚民[1,2] 徐晓虹[1,2] 张婧[1,2] 罗清清[1] 叶银萍[1,2] 

机构地区：[1]浙江师范大学化学与生命科学学院,浙江金华321004 [2]浙江师范大学生态研究所,浙江金华321004

出　　处：《生物物理学报》2009年第6期423-429,共7页Acta Biophysica Sinica

基　　金：国家自然科学基金(30771783;30872087);浙江省自然科学基金重点项目(Z2090955)资助~~

摘　　要：为了探讨环境雌激素双酚A(bisphenol-A,BPA)对子代发育期脑内雌激素受体(estrogen receptor,ER)和芳香化酶P450arom表达的影响,对妊娠第7天至哺乳期(仔鼠出生后21天)的母鼠灌胃染毒BPA(200、50、5、0.5mg·kg-1/d),用Western-blot法分别检测出生后4、7、14、21、56天雄性仔鼠的海马及前皮层ERβ和P450arom蛋白表达。结果显示,BPA剂量依赖性地上调前皮层和海马P450arom表达,抑制ERβ蛋白表达。在皮层,出生后4～56天各时间点的P450arom和ERβ表达对BPA都很敏感,其中200、50或5mg·kg-1/dBPA组与对照组相比有显著差异(P<0.05,P<0.01或P<0.001);在海马内,BPA对生后发育早期P450arom和ERβ表达的影响更为明显,出生后2周内,200和50mg·kg-1/dBPA组与对照组相比有显著差异(P<0.05,P<0.01或P<0.001)。以上结果提示,母体围产期BPA暴露可通过上调P450arom而促进雄性子鼠皮层和海马的雌激素合成,并由此抑制ERβ表达。这可能是BPA影响雄性子代脑发育的机制之一。The purpose of the present study is to investigate the effects of perinatal maternal exposure to bisphenol-A （BPA） on the estrogen receptor beta （ERβ） and P450arom expressions of brain in male offspring rats. Dams were orally exposed to BPA dissolved in oil （200, 50, 5 or 0.5 mg·kg^-1/d） or only oil as a vehicle control per day from gestational day 7 through postnatal day （PND） 21. Western-blotting technique was used to determine the expressions of ERβ and P450arom in the premotor cortex and the hippocampus of male offspring rats at PND 4, 7, 14, 21, 56. The results showed that BPA dosage-dependently up-regulated the expression of the P450arom but down-regulated the expression of ERβ in both the premotor cortex and the hippocampus. In the premotor cortex, P450arom and ERβ expressions were sensitive to BPA during postanal day 4 through day 56, and BPA-treated groups at 200, 50, or 5 mg·kg^-1/d displayed significant different compared to the control group （P〈0.05, P〈0.01, or P〈0.001）. In the hippocampus, the affects of BPA on the expressions of P450arom and ERβ were more marked during the early postnatal stage, and BPA groups of 200 or 50 mg·kg^-1/d showed significant different compared to the control group （P〈0.05, P〈0.01 or P〈0.001）. These results suggest that perinatal exposure to BPA enhanced the synthesis of estrogen through up-regulating the expression of P450arom in the premotor cortex and the hippocampus, thereby inhibiting the expression of ERβ. This may be one of the mechanisms underlying the effects of BPA on the development of brain.

关 键 词：双酚A 雌激素Β受体 芳香化酶P450arom 前皮层 海马 

分 类 号：Q735[生物学—分子生物学]