邻苯二甲酸酯暴露与氧化应激生物标志物之间的性别关联：一项前瞻性队列研究

Gender associations between phthalate exposure and biomarkers of oxidative stress: A prospective cohort study

邻苯二甲酸酯暴露与氧化应激生物标志物之间的性别关联：一项前瞻性队列研究

Authors: Jian-Qing Wang,Zhi-Juan Li,Hui Gao,Jie Sheng,Chun-Mei Liang,Ya-Bin Hu,Xun Xia,Kun Huang,Su-Fang Wang,Peng Zhu,Jia-Hu Hao,Fang-Biao Tao

Source: Wang JQ, Li ZJ, Gao H, et al. Gender associations between phthalate exposure and biomarkers of oxidative stress: A prospective cohort study.ToxicolIndHealth.2024;40(6):312-322. doi:10.1177/07482337241245453.

Abstract

Previous epidemiologic research has shown that phthalate exposure in pregnant women is related to adverse birth outcomes in a sex-specific manner. However, the biological mechanism of phthalate exposure that causes these birth outcomes remains poorly defined. In this research, we investigated the association between phthalate exposure and placental oxidative stress in a large population-based cohort study, aiming to initially explore the relationship between phthalate exposure and gene expression in placental oxidative stress in a sex-specific manner. Quantitative PCR was performed to measure the expression of placental inflammatory mRNAs (HO-1, HIF1α, and GRP78) in 2469 placentae. The multiple linear regression models were used to investigate the associations between mRNA and urinary phthalate monoesters. Phthalate metabolites monomethyl phthalate (MMP) and mono-n-butyl phthalate (MBP) were positively correlated with higher HIF1α expression in placentae of male fetuses (p < .05). Mono-benzyl phthalate (MBzP) increased the expression of HO-1, HIF1α, and GRP78 in placentae of male fetuses, and mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) up-regulated the expression of HIF1α and GRP78. Additionally, mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP) was negatively correlated with HO-1, HIF1α, and GRP78 in placentae of female fetuses. Maternal phthalate exposure was associated with oxidative stress variations in placental tissues. The associations were closer in the placentas of male fetuses than in that of female ones. The placenta oxidative stress is worth further investigation as a potential mediator of maternal exposure-induced disease risk in children.

先前的流行病学研究表明，孕妇接触邻苯二甲酸酯与不良分娩结局有关，具有性别特异性。然而，邻苯二甲酸酯暴露导致这些出生结局的生物学机制仍然不明确。在这项研究中，我们在一项基于人群的大型队列研究中调查了邻苯二甲酸酯暴露与胎盘氧化应激之间的关联，旨在以性别特异性的方式初步探索邻苯二甲酸酯暴露与胎盘氧化应激基因表达之间的关系。定量PCR检测2469例胎盘中胎盘炎性mRNA（HO-1、HIF1α和GRP78）的表达。采用多元线性回归模型研究mRNA与尿邻苯二甲酸酯单酯的相关性。邻苯二甲酸酯代谢物邻苯二甲酸单甲酯（MMP）和邻苯二甲酸单正丁酯（MBP）与男性胎儿胎盘中较高的HIF1α表达呈正相关（p < .05）。邻苯二甲酸单苄酯（MBzP）增加男性胎儿胎盘中HO-1、HIF1α和GRP78的表达，邻苯二甲酸单（2-乙基-5-羟基己基）酯（MEHHP）上调HIF1α和GRP78的表达。此外，邻苯二甲酸单（2-乙基-5-氧代己基）酯（MEOHP）与女性胎儿胎盘中的HO-1、HIF1α和GRP78呈负相关。母体邻苯二甲酸酯暴露与胎盘组织的氧化应激变化有关。男性胎儿胎盘的关联比女性胎儿的胎盘更紧密。胎盘氧化应激作为母亲暴露诱发的儿童疾病风险的潜在介质，值得进一步研究。