Department of Environmental Health Sciences, University of Michigan School of Public Health,Ann Arbor, MI, USA.
Graduate School of Public Health, University of Puerto Rico, San Juan, PR, USA.
Sci Total Environ. 2023 Jan 1;854:158773. doi: 10.1016/j.scitotenv.2022.158773. Epub 2022 Sep 13.
Phthalates are ubiquitous environmental exposures that may be implicated in inflammatory processes, as demonstrated by previous in vivo and in vitro studies. Few human studies have substantiated these observations. This study sought to examine whether maternal phthalate exposures impact inflammatory processes, as measured by circulating inflammatory biomarkers, in the PROTECT cohort in northern Puerto Rico. Inflammatory biomarkers included matrix metalloproteinases 1, 2, and 9 (MMPs), C-reactive protein (CRP), vascular cell adhesion molecule-1 (VCAM), and intercellular cell adhesion molecule-1 (ICAM). Biomarkers were measured in maternal serum samples collected during pregnancy. 19 phthalate metabolites were assessed in urinary samples collected at three study visits across pregnancy. Phthalates with <50 % of measurements above the limit of detection were excluded from analysis. We utilized linear mixed effect models to estimate associations between interquartile range increases in phthalate metabolite concentrations and percent changes in inflammatory biomarkers. Our results revealed significant associations between mono-n-butyl phthalate (MBP) and higher MMP1 by 7.86 % (95 % CI: 0.49, 15.76) and between mono oxononyl phthalate (MONP) and higher MMP2 by 8.30 % (95 % CI: 2.22, 14.75). We observed negative or null associations between phthalate metabolites and MMP2, MMP9, ICAM, VCAM, and CRP. Many results were significantly modified by fetal sex, particularly those between di-2-ethylhexyl phthalate (DEHP) metabolites and MMP1 (p-interaction: MEHHP = 0.01, MEOHP = 0.04, MECPP = 0.01) and MMP2 (p-interaction: MEHHP = 0.03, MEOHP = 0.01, MECPP = 0.01), for which associations were positive among only women carrying female fetuses. MMPs have been previously associated with preeclampsia and hypertensive pregnancy disorders as mediators of artery remodeling. Hence, our findings suggest a potential role for phthalates in mediating the maternal inflammatory response, as well as significant sexual dimorphism in these relationships, which has implications for several adverse pregnancy outcomes.
邻苯二甲酸酯是普遍存在于环境中的暴露物，先前的体内和体外研究表明，它们可能与炎症过程有关。很少有人类研究证实了这些观察结果。本研究旨在探讨波多黎各北部 PROTECT 队列中，母体邻苯二甲酸酯暴露是否会影响循环炎症生物标志物所测量的炎症过程。炎症生物标志物包括基质金属蛋白酶 1、2 和 9（MMPs）、C 反应蛋白（CRP）、血管细胞黏附分子-1（VCAM）和细胞间黏附分子-1（ICAM）。生物标志物在妊娠期间采集的母体血清样本中进行测量。在妊娠期间的 3 次研究访问中采集尿液样本，检测了 19 种邻苯二甲酸酯代谢物。排除了检测不到 50%的测量值的邻苯二甲酸酯进行分析。我们利用线性混合效应模型来估计邻苯二甲酸酯代谢物浓度的四分位间距增加与炎症生物标志物的百分比变化之间的关联。我们的研究结果表明，单正丁基邻苯二甲酸酯（MBP）与 MMP1 升高 7.86%（95%CI：0.49，15.76）之间存在显著关联，单氧壬基邻苯二甲酸酯（MONP）与 MMP2 升高 8.30%（95%CI：2.22，14.75）之间存在显著关联。我们观察到邻苯二甲酸酯代谢物与 MMP2、MMP9、ICAM、VCAM 和 CRP 之间呈负相关或无关联。许多结果都受到胎儿性别显著的影响，特别是二-2-乙基己基邻苯二甲酸酯（DEHP）代谢物与 MMP1（p 相互作用：MEHHP=0.01，MEOHP=0.04，MECPP=0.01）和 MMP2（p 相互作用：MEHHP=0.03，MEOHP=0.01，MECPP=0.01）之间的关联，仅在携带女胎的女性中呈阳性。MMPs 先前与子痫前期和高血压妊娠疾病有关，作为动脉重塑的介质。因此，我们的研究结果表明，邻苯二甲酸酯在介导母体炎症反应中可能具有潜在作用，并且这些关系存在显著的性别二态性，这对几种不良妊娠结局有影响。
