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孕期 PM 暴露可诱导大鼠子宫雌激素受体启动子区域超甲基化,并降低后代出生体重。

PM exposure during pregnancy induces hypermethylation of estrogen receptor promoter region in rat uterus and declines offspring birth weights.

机构信息

Division of Neonatology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China.

Department of Genetics, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, 710061, China.

出版信息

Environ Pollut. 2018 Dec;243(Pt B):851-861. doi: 10.1016/j.envpol.2018.09.065. Epub 2018 Sep 15.

DOI:10.1016/j.envpol.2018.09.065
PMID:30245447
Abstract

Particulate matter 2.5 (PM) exposures during pregnancy could lead to declined birth weight, intrauterine developmental restriction, and premature delivery, however, the underlying mechanisms are still not elucidated. There are few studies concerning the effects of PM exposure on maternal and child health in Xi'an (one of the cities with severe air pollution of PM in North China). Then, this study aimed to investigate the effect of PM exposure in Xi'an on the offspring birth weights and the possibly associated epigenetic mechanisms. We found the Low and High groups: the offspring with declined birth weights; the decreased mRNA and protein expression of the estrogen receptor (ERs) and eNOs in the uterus; the decreased endometria vascular diameter maximum (EVDM); the increased mRNA and protein expressions of the DNMT1 and 3b in the uterus; the elevated methylation levels of the CpG sites in the CpG island of ERα promoter region in the uterus. However, no differences were observed in the mRNA or protein expressions of ERβ and DNMT3a between the Clean and PM exposure groups, as well as endometriavascular density (EVD). Additionally, PM level was negatively correlated with the ERα protein expression, EVDM and offspring birth weight, as well as the methylation level of the CpG sites in the CpG island of ERα promoter region and the ERα protein expression in the uterus; whereas the ERα protein expression was positively correlated with the offspring birth weight, as well as PM level and the methylation level of the CpG sites in the CpG island of ERα promoter region in the uterus. Taken together, elevated methylation level of the CpG sites in the CpG island of ERα promoter region reduces ERα expression in the uterus, which could be one of the epigenetic mechanisms that pregnant PM exposure reduces the offspring birth weights.

摘要

颗粒物 2.5(PM)暴露在怀孕期间可能导致出生体重下降、宫内发育受限和早产,但潜在机制尚不清楚。在中国北方 PM 污染严重的城市之一——西安,关于 PM 暴露对母婴健康影响的研究较少。因此,本研究旨在探讨西安 PM 暴露对后代出生体重的影响及其可能相关的表观遗传机制。我们发现了低和高两组:出生体重下降的后代;子宫中雌激素受体(ERs)和 eNOs 的 mRNA 和蛋白表达降低;子宫内膜血管最大直径(EVDM)降低;子宫中 DNMT1 和 3b 的 mRNA 和蛋白表达增加;子宫中 ERα 启动子区 CpG 岛的 CpG 位点甲基化水平升高。然而,在清洁和 PM 暴露组之间,子宫中 ERβ 和 DNMT3a 的 mRNA 或蛋白表达以及子宫内膜血管密度(EVD)没有差异。此外,PM 水平与 ERα 蛋白表达、EVDM 和后代出生体重呈负相关,与子宫中 ERα 启动子区 CpG 岛的 CpG 位点甲基化水平和 ERα 蛋白表达呈负相关;而 ERα 蛋白表达与后代出生体重呈正相关,与 PM 水平和子宫中 ERα 启动子区 CpG 岛的 CpG 位点甲基化水平呈正相关。总之,ERα 启动子区 CpG 岛的 CpG 位点甲基化水平升高降低了子宫中 ERα 的表达,这可能是 PM 暴露降低后代出生体重的表观遗传机制之一。

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