Barrett Emily S, Skrill David, Zhou Elaine, Thurston Sally W, Girardi Theresa, Brunner Jessica, Liang Hai-Wei, Miller Richard K, Salafia Carolyn M, O'Connor Thomas G, Adibi Jennifer J
Department of Biostatistics and Epidemiology, Rutgers School of Public Health, Piscataway, NJ, USA; Environmental and Occupational Health Sciences Institute, Rutgers University, Piscataway, NJ, USA; Department of Obstetrics and Gynecology, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.
Department of Biostatistics and Computational Biology, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.
Sci Total Environ. 2025 Jan 1;958:178116. doi: 10.1016/j.scitotenv.2024.178116. Epub 2024 Dec 17.
Pregnant people are ubiquitously exposed to endocrine-disrupting phthalates through consumer products and food. The placenta may be particularly vulnerable to the adverse effects of phthalates, with evidence from animal models suggesting impacts on placental development and vascularization. We translate this research to humans, examining gestational exposure to phthalates and phthalate replacements in relation to novel markers of chorionic plate surface vascularization. Phthalate and phthalate replacement metabolites were measured in first trimester urine from pregnant participants in the Understanding Pregnancy Signals and Infant Development (UPSIDE) cohort (n = 154). At delivery, placentae underwent specialized 2D and 3D digital imaging to quantify chorionic plate surface vasculature. Using weighted quantile g-computation mixtures methods as well as multivariable linear regression models examining individual metabolites, we evaluated associations with overall chorionic plate surface area and five chorionic plate surface vascular measures, adjusting for covariates. We additionally examined interactions with placental sex. Exposure to a phthalate mixture was associated with longer total arterial arc length (β = 9.64 cm; 95%CI: 1.68, 17.59), shorter mean arterial arc length (β = -0.07 cm; 95%CI: -0.14, -0.01), and more arterial branch points (β = 5.77; 95%CI: 1.56, 9.98), but not chorionic plate surface area. In models considering individual metabolites and their molar sums, results were strongest for the metabolites of Di-isobutyl phthalate (DiBP), Di-isononyl phthalate (DiNP), and Di(2-ethylhexyl) phthalate (DEHP). Associations with metabolites of phthalate replacements tended to be in the same direction but weaker. Few sex differences were observed. Gestational phthalate exposure may be associated with alterations in placental chorionic plate surface vasculature characterized by more branching and shorter segments. These alterations may have implications for placental perfusion and suggest a placental mechanism by which phthalates may impact fetal development.
孕妇通过消费品和食物普遍接触到具有内分泌干扰作用的邻苯二甲酸盐。胎盘可能对邻苯二甲酸盐的不良影响尤为敏感，动物模型的证据表明其对胎盘发育和血管形成有影响。我们将这项研究转化到人类身上，研究孕期邻苯二甲酸盐及其替代物的暴露与绒毛膜板表面血管形成新标志物之间的关系。在“了解妊娠信号与婴儿发育”（UPSIDE）队列研究中，对154名孕妇孕早期尿液中的邻苯二甲酸盐及其替代物代谢物进行了测量。分娩时，胎盘接受了专门的二维和三维数字成像，以量化绒毛膜板表面的脉管系统。我们使用加权分位数g计算混合方法以及检查单个代谢物的多变量线性回归模型，评估了与绒毛膜板总面积和五项绒毛膜板表面血管测量指标的关联，并对协变量进行了调整。我们还研究了与胎盘性别的相互作用。接触邻苯二甲酸盐混合物与总动脉弧长较长（β = 9.64厘米；95%置信区间：1.68，17.59）、平均动脉弧长较短（β = -0.07厘米；95%置信区间：-0.14，-0.01）以及动脉分支点较多（β = 5.77；95%置信区间：1.56，9.98）有关，但与绒毛膜板表面积无关。在考虑单个代谢物及其摩尔总和的模型中，邻苯二甲酸二异丁酯（DiBP）、邻苯二甲酸二异壬酯（DiNP）和邻苯二甲酸二（2-乙基己基）酯（DEHP）的代谢物结果最为显著。与邻苯二甲酸盐替代物代谢物的关联往往方向相同但较弱。未观察到明显的性别差异。孕期邻苯二甲酸盐暴露可能与胎盘绒毛膜板表面脉管系统的改变有关，其特征为分支增多和节段变短。这些改变可能对胎盘灌注有影响，并提示邻苯二甲酸盐可能影响胎儿发育的一种胎盘机制。
