摘要
为探究母鼠妊娠期暴露双酚A(bisphenol A,BPA)对子代雌鼠生殖激素的影响及BPA与机体发生作用的分子机制。通过灌服不同剂量的BPA制造孕鼠BPA暴露模型,然后计算子代小鼠断乳时的死亡率、卵巢与子宫系数;放射免疫法检测血清中雌二醇(E2)、孕酮(P4)、卵泡刺激素(FSH)、黄体生成素(LH)水平;酶联免疫吸附试验(ELISA)检测血清雌激素受体α(ERα)、雌激素受体β(ERβ)含量;qPCR法检测卵巢DNA甲基转移酶1(Dnmt1),DNA甲基转移酶3A(Dnmt3A),DNA甲基转移酶3B(Dnmt3B),孕酮受体(PgR)及雌激素受体α(EsR1)mRNA表达。结果显示,子代雌鼠的相关指标与母鼠妊娠期BPA暴露存在非单调性剂量-反应关系;卵巢系数、E2含量与BPA剂量呈现“U”型关系;子宫系数,血清P4、FSH、LH水平,卵巢ERβ含量,卵巢Dnmt1、Dnmt3A、Dnmt3BmRNA相对转录水平与BPA剂量呈现“波浪式”关系;卵巢PgR、EsR1mRNA相对转录水平与BPA剂量呈现“倒U”型关系;且BPA暴露组与空白组相比有极显著差异(P<0.01)。这表明BPA可能通过增强子代雌鼠DNA甲基化酶的转录活性使生殖激素分泌紊乱,造成子代生殖损伤。
To investigate the effects of exposure to bisphenol A(BPA)on the reproductive hormones of offspring females and the molecular mechanism of BPA,animal model of pregnant mice was prepared by gavaging different doses of BPA.Then the mortality and the ovarian and uterus index of the offspring weanling females were calculated.The contents of serum estradiol(E2),progesterone(P4),follicle stimulating hormone(FSH),luteinizing hormone(LH)levels were detected by radioimmunoassay.The contents of serum estrogen receptor alpha(ERα)and estrogen receptor beta(ERβ)were detected by enzyme-linked immunosorbent assay(ELISA).The relative transportation expression of DNA methyltransferase 1(Dnmt1),DNA methyltransferase 3A(Dnmt3A),DNA methyltransferase 3B(Dnmt3B),progesterone receptor(PgR)and estrogen receptor alpha(EsR1)mRNA in the ovary were detected by real-time quantitative PCR(qPCR).The results showed a non-monotonic dose-response relationship between BPA and offspring females.With the increase of dose,the ovarian index and serum E2content showed a“U”shape relationship,and the uterus index,the serum P4,FSH,LH,ovarian ERβlevels and the mRNA levels of Dnmt1,Dnmt3A,Dnmt3BmRNA showed a“wave”relationship,the mRNA levels of PgR,EsR1showed an“inverted U”relationship.There was a significant difference between the control group and BPA group(P<0.01).It indicated that BPA may cause reproductive hormone secretion disorder by enhancing the transcriptional activity of DNA methyltransferase in offspring wealing females,causing reproductive damage.
作者
魏媛媛
李淑颖
崔宇擎
耿玉萌
钟秀会
包永占
史万玉
WEI Yuan-yuan;LI Shu-ying;CUI Yu-qing;GENG Yu-meng;ZHONG Xiu-hui;BAO Yongzhan;SHI Wang-yu(College of Traditional Chinese Veterinary Medicine,Hebei Agricultural University,Baoding,Hebei 071000,China;Center for Traditional Chinese Veterinary Medicine Engineering Technology of Hebei,Baoding,Hebei 071000,China)
出处
《中国兽医学报》
CAS
CSCD
北大核心
2019年第12期2422-2428,共7页
Chinese Journal of Veterinary Science
基金
国家自然科学基金资助项目(31872506)
