PM2.5 exposure during pregnancy induces hypermethylation of estrogen receptor promoter region in rat uterus and declines offspring birth weights

摘要

Particulate matter 2.5 (PM2.5) 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 PM2.5 exposure on maternal and child health in Xi'an (one of the cities with severe air pollution of PM2.5 in North China). Then, this study aimed to investigate the effect of PM2.5 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 DNMTI and 3b in the uterus; the elevated methylation levels of the CpG sites in the CpG island of ER alpha promoter region in the uterus. However, no differences were observed in the mRNA or protein expressions of ER beta and DNMT3a between the Clean and PM2.5 exposure groups, as well as endometriavascular density (EVD). Additionally, PM2.5 level was negatively correlated with the ERa protein expression, EVDM and offspring birth weight, as well as the methylation level of the CpG sites in the CpG island of ER alpha promoter region and the ER alpha protein expression in the uterus; whereas the ER alpha protein expression was positively correlated with the offspring birth weight, as well as PM2.5 level and the methylation level of the CpG sites in the CpG island of ER alpha promoter region in the uterus. Taken together, elevated methylation level of the CpG sites in the CpG island of ER alpha promoter region reduces ER alpha expression in the uterus, which could be one of the epigenetic mechanisms that pregnant PM2.5 exposure reduces the offspring birth weights. (C) 2018 Elsevier Ltd. All rights reserved.