甲基汞暴露对子代生长发育的影响——基于DNA甲基化研究  

Effects of methylmercury exposure on the growth and development of offspring based on DNA methylation

作　　者：文甫利 刘浩浩 陈芳 杨劭晨 冯琳 王文娟[1] 李平 WEN Fu-li;LIU Hao-hao;CHEN Fang;YANG Shao-chen;FENG Lin;WANG Wen-juan;LI Ping(School of Public Health,the Key Laboratory of Environmental Pollution Monitoring and Disease Control,Ministry of Education,Guizhou Medical University,Guiyang,Guizhou 550025,China;不详)

机构地区：[1]贵州医科大学公共卫生与健康学院,环境污染与疾病监控教育部重点实验室,贵州贵阳550025 [2]中国科学院地球化学研究所环境地球化学国家重点实验室,贵州贵阳550081

出　　处：《现代预防医学》2023年第9期1572-1577,共6页Modern Preventive Medicine

基　　金：国家自然科学基金(U1812403);环境污染与疾病监控教育部重点实验室开放课题(GMU-2020-HJZ-04)。

摘　　要：目的本研究基于DNA甲基化,探讨甲基汞(MeHg)暴露对子代生长发育的影响。方法通过面对面问卷调查获取研究对象基本信息,系统采集万山汞矿区114位分娩母亲的静脉血、新生儿脐带血和生长发育指标。将24只妊娠SD大鼠随机分为对照组(生理盐水)、低(0.6 mg/kg)、中(1.2 mg/kg)、高(2.4 mg/kg)剂量MeHg染毒组,自受孕第5天灌胃染毒至子代仔鼠出生第21天(PND21),适应性喂养至PND60天。利用液相色谱-串联质谱法测量新生儿脐带血和仔鼠血5-甲基胞嘧啶(5mC)和5-羟甲基胞嘧啶(5hmC)水平。结果暴露组新生儿的体重(t=2.025,P=0.045)和双顶径(t=2.382,P=0.019)均显著低于对照组。与对照组相比,暴露组脐带血5mC(t=2.615,P=0.010)和5hmC(t=3.640,P<0.001)均显著下降。脐带血5mC与新生儿股骨长之间呈显著正相关(r=0.197,P=0.035)。动物实验结果显示,各剂量染毒组仔鼠体重组间差异有统计学意义(F=11.327,P<0.001);与对照组相比,低、中、高剂量组仔鼠平均体重显著降低,差异均有统计学意义(均P<0.05);高剂量组仔鼠平均体重低于中剂量组(P<0.05)。随染毒剂量的增加,仔鼠5mC(F=7.254,P=0.002)和5hmC(F=11.609,P<0.001)均降低;与对照组相比,中、高剂量组仔鼠5mC平均水平降低,低、中、高剂量组仔鼠5hmC平均水平均降低,差异均有统计学意义(均P<0.05);高剂量组仔鼠5mC和5hmC平均水平均较低剂量组低(均P<0.05)。仔鼠5mC、5hmC与体重之间均呈显著正相关(r=0.472,P=0.020;r=0.651,P=0.001)。结论全基因组DNA甲基化和羟甲基化水平偏低可能在MeHg暴露抑制子代生长发育中起到重要作用。Objective To explore the effects of methylmercury(MeHg)exposure on the growth and development of offspring based on DNA methylation.Methods Questionnaires were designed to obtain general information of participants during face-to-face surveys,and venous blood of 114 mothers and their newborn’s umbilical cord blood(UCB)and growth and development indicators were systematically collected in Wanshan Mercury Mining Area.A total of 24 pregnant SD rats were randomly divided into control group(normal saline),low-dose(0.6 mg/kg),medium-dose(1.2 mg/kg),and high-dose(2.4 mg/kg)MeHg exposure groups.The rats were given by gavage from the fifth day of conception to postnatal day 21(PND21)and then adaptively fed to PND60.The levels of 5-methylcytosine(5mC)and 5-hydroxymethylcytosine(5hmC)in the blood of newborns and offspring rats were measured by liquid chromatography-mass spectrometry.Results The weight(t=2.025,P=0.045)and biparietal diameter(t=2.382,P=0.019)of newborns in exposure group were significantly lower than those in control group.Compared with control group,5mC(t=2.615,P=0.010)and 5hmC(t=3.640,P<0.001)of UCB in exposure group decreased significantly.There was significantly positive correlation between 5mC and neonatal femoral length(r=0.197,P=0.035).The results of rat experiments showed that the body weight of offspring rats revealed significant difference among MeHg exposure groups(F=11.327,P<0.001).Compared with the control group,the average body weight of offspring rats in low-dose,medium-dose,and high-dose groups decreased with statistically significant difference(all P<0.05).The average body weight of offspring rats in high-dose group was lower than that in medium-dose group(P<0.05).With the increase of the exposure doses,the 5mC(F=7.254,P=0.002)and 5hmC(F=11.609,P<0.001)of offspring rats were reduced.The average 5mC of offspring rats in medium-dose and high-dose groups,and the average 5hmC of offspring rats in low-dose,medium-dose,and high-dose groups were significantly lower compared with the control group,

关 键 词：甲基汞暴露 DNA甲基化 新生儿 仔鼠 生长发育 

分 类 号：R114[医药卫生—卫生毒理学]