Department of Pediatrics, Zibo Central Hospital, Shandong Province, 255000, China.
Department of Thoracic Surgery, Huantai Country People's Hospital, Shandong Province, 255000, China.
Reprod Biol. 2021 Dec;21(4):100574. doi: 10.1016/j.repbio.2021.100574. Epub 2021 Nov 15.
Polycyclic aromatic hydrocarbons (PAHs), as a kind of endocrine disruptors, can enter the fetus body cross the placental barrier from prenatal PAHs exposure to cause adverse birth outcomes. However, it is controversial association between prenatal PAHs exposure and low birth weight (LBW) of their infants. So the present study aimed to estimate the effects of prenatal PAHs exposure during the pregnancy on the risk of LBW in a Chinese cohort through modifying the DNA methylation states. A longitudinal prospective study with 407 pregnant women was established from May to October 2019. The prenatal PAHs exposure during the pregnancy was assessed using the internal dose such as the PAHs metabolites and PAH-DNA adducts in the umbilical cord blood. The methylation levels of genomic DNA and growth-related genes (IGF1 and IGF2) were assessed, while the expressions of these genes were both determined by RT-PCR and Elisa methods. The growth outcomes and relevant Z-scores were recorded at birth. The correlations between the DNA methylation status and concentrations of PAHs, expression levels of growth-related genes and body weight/WAZ were investigated as the measures. According to the PAH-DNA adducts, the subjects were divided into two groups: PAHs-exposed group (PAH-DNA adducts>0, n = 55) and non-exposed group (PAH-DNA adducts = 0, n = 352). Compared with the non-exposed group, it displayed marked decreased birth weight, and increased concentrations of PAHs and DNA methylation levels of the global genomic, IGF1 and IGF2 with their lower expressions in the PAHs-exposed group. These hypermethylation (global genomic, CpG14 and CpG15 of IGF1, and CpG14 of IGF2) were positively correlated with the contents of PAHs in the umbilical cord blood, and negatively correlated with the growth outcomes and their expressions. Totally, prenatal PAHs exposures may contribute to an increased risk of LBW of their infants by modulating the DNA methylation states of genomic DNA and growth-related genes (IGF1 and IGF2) in the umbilical cord blood, which could provide the prenatal prevention of PAHs exposure from possible environmental media except from the occupation and tobacco usage to ensure the health of their infants.
多环芳烃(PAHs)作为一种内分泌干扰物,可通过胎盘屏障进入胎儿体内,导致产前 PAHs 暴露对不良出生结局的影响。然而,产前 PAHs 暴露与低出生体重(LBW)之间的关联仍存在争议。因此,本研究旨在通过修饰 DNA 甲基化状态,评估妊娠期间产前 PAHs 暴露对中国队列中 LBW 风险的影响。一项前瞻性纵向研究于 2019 年 5 月至 10 月期间纳入了 407 名孕妇。采用内剂量(脐带血中 PAHs 代谢物和 PAH-DNA 加合物)评估妊娠期间的 PAHs 暴露情况。评估了基因组 DNA 和生长相关基因(IGF1 和 IGF2)的甲基化水平,同时通过 RT-PCR 和 Elisa 方法测定了这些基因的表达。在出生时记录了生长结果和相关 Z 评分。研究了 DNA 甲基化状态与 PAHs 浓度、生长相关基因表达水平与体重/WAZ 之间的相关性。根据 PAH-DNA 加合物,将受试者分为两组:PAHs 暴露组(PAH-DNA 加合物>0,n=55)和非暴露组(PAH-DNA 加合物=0,n=352)。与非暴露组相比,PAHs 暴露组的出生体重明显降低,PAHs 浓度升高,基因组、IGF1 及其 CpG14 和 CpG15 、IGF2 的 CpG14 等基因的 DNA 甲基化水平降低,其表达水平也降低。这些过度甲基化(基因组、IGF1 的 CpG14 和 CpG15 、IGF2 的 CpG14)与脐带血中 PAHs 的含量呈正相关,与生长结果及其表达呈负相关。总之,产前 PAHs 暴露可能通过调节脐带血中基因组 DNA 和生长相关基因(IGF1 和 IGF2)的 DNA 甲基化状态,增加婴儿 LBW 的风险,这为从职业和烟草使用等可能的环境介质中预防产前 PAHs 暴露提供了可能,以确保婴儿的健康。