重金属宫内暴露对胎儿<i>DNMT3B</i>基因甲基化的影响

摘要
图/表
参考文献
相关文章 (11)

全文: PDF (845 KB) HTML (32 KB)
输出: BibTeX | EndNote (RIS)

摘要目的分析胎儿宫内暴露重金属与脐带血中DNA甲基转移酶3B(DNMT3B)基因甲基化的关系。方法本研究基于在山西开展的病例对照研究,共纳入173例无重大体表出生缺陷胎儿。采用电感耦合等离子体质谱(ICP-MS)仪检测脐带组织中砷(As)、铅(Pb)、镉(Cd)、镍(Ni)四种重金属的含量,采用MassARRAY时间飞行质谱阵列基因分析平台检测脐带血中DNMT3B的甲基化水平。运用多重线性回归模型分析重金属暴露对DNMT3B甲基化的影响。结果脐带组织中砷、铅、镉、镍含量中位值及四分位间距分别为7.66 (5.24-10.30) ng/g、23.91 (16.74-44.29) ng/g、0.95 (0.47-2.71) ng/g、21.42 (15.61-32.2) ng/g。脐带血中DNMT3B基因甲基化水平为(7.38±2.66)%。脐带组织镉对DNMT3B甲基化水平有影响(β=0.74, P=0.03),镉与砷、铅、镍对DNMT3B甲基化水平的影响均无交互作用。结论脐带组织重金属暴露会影响胎儿DNMT3B的甲基化水平。

	服务

	把本文推荐给朋友
	加入我的书架
	加入引用管理器
	E-mail Alert
	RSS
	作者相关文章
	杨文蕾
	倪文丽
	田甜
	于锦慧
	靳蕾
	任爱国
	王琳琳

关键词 ：重金属, 脐带, 甲基化, DNMT3B

Abstract：Objective To investigate the relationship between concentration of heavy metals in umbilical cord and DNA methyltransferase gene (DNMT3B) methylation in cord blood. Methods This study was based on the case-control study conducted in Shanxi province, a total of 173 non-malformed infants were recruited in our analysis. Concentrations of arsenic (As), lead (Pb), cadmium (Cd) and nickel (Ni) in umbilical cord tissues were measured by inductively coupled plasma mass spectrometry (ICP-MS). The methylation level of DNMT3B gene in cord blood was determined by MassARRAY time-flight mass spectrometry array gene analysis platform. Multivariable liner regression models were used to analyze the effect of heavy metals on DNMT3B methylation status. Results The median (interquartile range) concentrations of As, Pb, Cd and Ni were 7.66 (5.24-10.30) ng/g, 23.91 (16.74-44.29) ng/g, 0.95 (0.47-2.71) ng/g and 21.42 (15.61-32.2) ng/g, respectively. The average methylation level of DNMT3B was (7.38±2.66)%. Multiple linear regression models showed Cd in umbilical cord have a significant effect on DNMT3B methylation level (β=0.74, P=0.03). No significant interaction was found between Cd and As, Pb or Ni on DNMT3B methylation level. Conclusion Umbilical cord heavy metals exposure may affect fetal methylation level of DNMT3B.

Key words： Heavy metals umbilical cord methylation DNMT3B

收稿日期: 2019-01-28

基金资助:国家自然科学基金(81773441,81472987);科技部重大专项资助(2016YFC1000501)

通讯作者: 王琳琳(linlinwang@bjmu.edu.cn)

引用本文:

杨文蕾, 倪文丽, 田甜, 于锦慧, 靳蕾, 任爱国, 王琳琳. 重金属宫内暴露对胎儿DNMT3B基因甲基化的影响[J]. 中国生育健康杂志, 2021, 32(3): 243-246. YANG Wenlei, NI Wenlei, TIAN Tian, YU Jinghui, JIN Lei, REN Aiguo, WANG Linlin. Effect of in utero exposure to metals on methylation level of DNMT3B gene. Chinese Journal of Reproductive Health, 2021, 32(3): 243-246.

链接本文:

http://cjrh.bjmu.edu.cn/CN/ 或 http://cjrh.bjmu.edu.cn/CN/Y2021/V32/I3/243

1 Wu X,Cobbina SJ,Mao G,et al.A review of toxicity and mechanisms of individual and mixtures of heavy metals in the environment.Environ Sci Pollut Res Int,2016,23:8244-8259.
2 Caserta D,Graziano A,Lo Monte G,et al.Heavy metals and placental fetal-maternal barrier:a mini-review on the major concerns.Eur Rev Med Pharmacol Sci,2013,17:2198-2206.
3 Punshon T,Davis MA,Marsit CJ,et al.Placental arsenic concentrations in relation to both maternal and infant biomarkers of exposure in a US cohort.J Expo Sci Environ Epidemiol,2015,25:599-603.
4 Thompson J,Bannigan J.Cadmium:toxic effects on the reproductive system and the embryo.Reprod Toxicol,2008,25:304-315.
5 Wang A,Holladay SD,Wolf DC,et al.Reproductive and developmental toxicity of arsenic in rodents:a review.Int J Toxicol,2006,25:319-331.
6 Martin EM,Fry RC.Environmental Influences on the epigenome:exposure- associated DNA methylation in human populations.Annu Rev Public Health,2018,39:309-333.
7 Marsit CJ.Influence of environmental exposure on human epigenetic regulation.J Exp Biol,2015,218:71-79.
8 朱江辉,任爱国.表观遗传流行病学.中国生育健康杂志,2009,20:378-382.
9 Maunakea AK,Chepelev I,Zhao K.Epigenome mapping in normal and disease States.Circ Res,2010,107:327-339.
10 Tajuddin SM,Amaral AF,Fernandez AF,et al.Genetic and non-genetic predictors of LINE-1 methylation in leukocyte DNA.Environ Health Perspect,2013,121:650-656.
11 Gribble MO,Tang WY,Shang Y,et al.Differential methylation of the arsenic (III) methyltransferase promoter according to arsenic exposure.Arch Toxicol,2014,88:275-282.
12 Goodrich JM,Sanchez BN,Dolinoy DC,et al.Quality control and statistical modeling for environmental epigenetics:a study on in utero lead exposure and DNA methylation at birth.Epigenetics,2015,10:19-30.
13 Vidal AC,Semenova V,Darrah T,et al.Maternal cadmium,iron and zinc levels,DNA methylation and birth weight.BMC Pharmacol Toxicol,2015,16:20.
14 Virani S,Rentschler KM,Nishijo M,et al.DNA methylation is differentially associated with environmental cadmium exposure based on sex and smoking status.Chemosphere,2016,145:284-290.
15 Sakamoto M,Yasutake A,Domingo JL,et al.Relationships between trace element concentrations in chorionic tissue of placenta and umbilical cord tissue:potential use as indicators for prenatal exposure.Environ Int,2013,60:106-111.
16 冯兰兰,梁春梅,黄锟,等.孕期和脐带血清砷水平及其与妊娠期高血压疾病关系.中国公共卫生,2018:1-3.
17 Okano M,Bell DW,Haber DA,et al.DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development.Cell,1999,99:247-257.
18 Hossain MB,Vahter M,Concha G,et al.Low-level environmental cadmium exposure is associated with DNA hypomethylation in Argentinean women.Environ Health Perspect,2012,120:879-884.
19 Jin X,Tian X,Liu Z,et al.Maternal exposure to arsenic and cadmium and the risk of congenital heart defects in offspring.Reprod Toxicol,2016,59:109-116.