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母体甲基化在产前气象条件与新生儿 H19/H19-DMR 甲基化关联中的作用。

The role of maternal methylation in the association between prenatal meteorological conditions and neonatal H19/H19-DMR methylation.

机构信息

Department of Environmental Health, School of Public Health, Zhengzhou University, Zhengzhou, Henan, 450001, PR China; Environment and Health Innovation Team, School of Public Health, Zhengzhou University, Zhengzhou, Henan, 450001, PR China.

Department of Environmental Health, School of Public Health, Zhengzhou University, Zhengzhou, Henan, 450001, PR China.

出版信息

Ecotoxicol Environ Saf. 2020 Jul 1;197:110643. doi: 10.1016/j.ecoenv.2020.110643. Epub 2020 Apr 18.

DOI:10.1016/j.ecoenv.2020.110643
PMID:32315786
Abstract

Meteorological conditions during pregnancy can affect birth outcome, which has been linked to the H19/H19-differentially methylated region (DMR). However, the detailed mechanisms underlying this association are unclear. This was investigated in the present study to provide epidemiological evidence for elucidating the pathogenesis of adverse birth outcomes. A total of 550 mother-newborn pairs were recruited in Zhengzhou, China from January 2010 to January 2012. Meteorological data including temperature (T), relative humidity (RH), and sunshine duration (SSD) were obtained from the China Meteorological Data Sharing Service System. Bisulfite sequencing PCR was performed to determine the methylation levels of H19/H19-DMR using genomic DNA extracted from maternal peripheral and umbilical cord blood. The results showed that H19-DMR methylation status in cord blood was positively associated with that in maternal blood. Neonatal H19-DMR methylation was negatively associated with T and RH during the first trimester and positively associated with these variables during the third trimester. There was a positive correlation between neonatal H19-DMR methylation and SSD during the second trimester and a negative correlation during the third trimester. Similar associations were observed between maternal H19-DMR methylation and prenatal meteorological conditions. We also observed significant interaction effects of maternal H19/H19-DMR methylation and most prenatal meteorological factors on neonatal methylation, and found that changes in the methylation status of maternal H19-DMR were responsible for the effects of prenatal meteorological conditions on neonatal methylation. In summary, neonatal H19-DMR methylation was significantly associated with prenatal meteorological conditions, which was modified and mediated by maternal H19-DMR methylation changes. These findings provide insights into the relationship between meteorological factors during pregnancy and adverse birth outcomes or disease susceptibility in offspring, and can serve as a reference for environmental policy-making.

摘要

妊娠期间的气象条件会影响分娩结果,而这与 H19/H19 差异甲基化区域(DMR)有关。然而,这种关联的具体机制尚不清楚。本研究旨在为阐明不良分娩结局的发病机制提供流行病学证据。2010 年 1 月至 2012 年 1 月,在中国郑州共招募了 550 对母婴。气象数据包括温度(T)、相对湿度(RH)和日照时间(SSD),均来自中国气象数据共享服务系统。采用 bisulfite 测序 PCR 法,用从母体外周血和脐血中提取的基因组 DNA 来测定 H19/H19-DMR 的甲基化水平。结果表明,脐带血中 H19-DMR 甲基化状态与母体血中 H19-DMR 甲基化状态呈正相关。新生儿 H19-DMR 甲基化与孕早期 T 和 RH 呈负相关,与孕晚期 T 和 RH 呈正相关。孕中期 H19-DMR 甲基化与 SSD 呈正相关,而孕晚期 H19-DMR 甲基化与 SSD 呈负相关。母体 H19-DMR 甲基化与产前气象条件也存在类似的相关性。我们还观察到母体 H19/H19-DMR 甲基化与大多数产前气象因素对新生儿甲基化的显著交互作用,发现母体 H19-DMR 甲基化状态的变化是产前气象条件对新生儿甲基化影响的原因。总之,新生儿 H19-DMR 甲基化与产前气象条件显著相关,这种相关性受到母体 H19-DMR 甲基化变化的修饰和介导。这些发现为妊娠期间气象因素与后代不良出生结局或疾病易感性之间的关系提供了新的认识,并可为环境政策制定提供参考。

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