母鼠孕期暴露双酚A对子代断乳雄鼠生殖内分泌以及睾丸DNA甲基化的影响  

Effects of bisphenol A expoused during pregnancy on reproductive endocrine and testicular DNA methylation in offspring weanling malemice

作　　者：魏媛媛 耿玉萌 李淑颖 钟秀会[1] 包永占[1,2] 史万玉 WEI Yuan-yuan;GENG Yu-meng;LI Shu-ying;ZHONG Xiu-hui;BAO Yong-zhan;SHI Wanyu(College of Traditional Chinese Veterinary Medicine,Agriculture University of Hebei,Baoding,Hebei 071000,China;Center for Traditional Chinese Veterinary Medicine Engineering Technology of Hebei,Baoding,Hebei 071000,China)

机构地区：[1]河北农业大学中兽医学院,河北保定071000 [2]河北省中兽药工程技术研究中心,河北保定071000

出　　处：《中国兽医学报》2019年第11期2260-2265,共6页Chinese Journal of Veterinary Science

基　　金：国家自然科学基金资助项目(31872506)

摘　　要：为探究母鼠妊娠期暴露双酚A(bisphenol A,BPA)对子代断乳雄鼠生殖内分泌与睾丸DNA甲基化的影响。按0,2.5,5.0,10.0,20.0,40.0mg·kg-1·d-1 BPA剂量在妊娠期(PND)1~17d灌胃孕鼠,制备孕鼠BPA暴露模型。然后统计母鼠妊娠期流产率,仔鼠断乳时存活率,睾丸系数。放射免疫法检测血清中雌二醇(E2)、睾酮(T)含量;酶联免疫吸附法检测血清中雌激素受体α(ERα)、雌激素受体β(ERβ)含量;实时定量荧光PCR法检测睾丸中DNA甲基转移酶1(Dnmt1)、DNA甲基转移酶3a(Dnmt3a)、DNA甲基转移酶3b(Dnmt3b)mRNA相对转录水平。结果显示,20.0mg/kg BPA暴露可极显著增加断乳时仔鼠睾丸系数(P<0.01);20.0,40.0mg/kg BPA暴露可显著增加母鼠流产率(P<0.05),极显著降低仔鼠存活率(P<0.01);2.5,20.0mg/kg BPA暴露可极显著提高仔鼠血清T和ERβ含量(P<0.01);各BPA剂量均可极显著降低仔鼠血清雌二醇水平(P<0.01),促进睾丸内Dnmt1转录,抑制Dnmt3a和Dnmt3b转录;血清中雌激素受体α含量与BPA剂量呈现非线性关系。表明BPA通过干扰子代雄鼠睾丸内DNA甲基转移酶(Dnmt)的转录,使睾酮、雌二醇及雌激素受体分泌紊乱,影响子代雄鼠的生殖机能。To investigate the effects of exposure to bisphenol A(BPA) on offspring male mice’ hormones and DNA methylation in testis.Pregnant mice were intragastrically administrated with 0,2.5,5.0,10.0,20.0,40.0 mg·kg-1·d-1BPA doses at 1-17 days of pregnancy(PND) to prepare a BPA exposure model.Then,the abortion rate of the pregnant rats,the survival rate of the weaned mice,and the testicular index were counted.The levels of estradiol(E2) and testosterone(T) in serum were detected by radioimmunoassay.Serum estrogen receptor alpha(ERα) and estrogen receptor beta(ERβ) levels were detected by enzyme-linked immunosorbent assay(ELISA).The relative transcription level of DNA methyltransferase1(Dnmt1),DNA methyltransferase3 a(Dnmt3 a),DNA methyltransferase3 b(Dnmt3 b) mRNA in the testis was detected by real-time quantitative PCR.The results showed that 20.0 mg/kg BPA significantly increased the testis index of the pups(P<0.01).Exposure to 20.0 mg/kg and 40.0 mg/kg BPA significantly increased the abortion rate of the mother(P<0.05),significantly reducing the survival rate of the pups(P<0.01),and the exposure of 2.5 mg/kg and 20.0 mg/kg BPA significantly increased the serum testosterone and ERβlevels(P<0.01),each BPA dose can significantly reduce serum estradiol levels in pups(P<0.01),nonlinear relationship with estrogen receptor alpha,and promote Dnmt1 transcription in testis,inhibit transcription of Dnmt3 aand Dnmt3 b.It indicates that BPA can interfere with the secretion of testosterone,estradiol and estrogen receptors by interfering with the transcription of DNA methyltransferase(Dnmt)in the testis of male offspring,affecting the reproductive health of the offspring.

关 键 词：双酚A DNA甲基转移酶 激素 

分 类 号：S859.8[农业科学—临床兽医学]