Program on Reproductive Health and the Environment, University of California, San Francisco (UCSF), San Francisco, California 94158.
Center for Reproductive Sciences and Department of Obstetrics, Gynecology & Reproductive Sciences, University of California, San Francisco (UCSF), San Francisco, California 94158.
Toxicol Sci. 2021 May 27;181(2):215-228. doi: 10.1093/toxsci/kfab028.
Perfluoroalkyl and polyfluoroalkyl substances (PFASs) and organophosphate flame retardants (OPFRs) are chemicals that may contribute to placenta-mediated complications and adverse maternal-fetal health risks. Few studies have investigated these chemicals in relation to biomarkers of effect during pregnancy. We measured 12 PFASs and four urinary OPFR metabolites in 132 healthy pregnant women during mid-gestation and examined a subset with biomarkers of placental development and disease (n = 62). Molecular biomarkers included integrin alpha-1 (ITGA1), vascular endothelial-cadherin (CDH5), and matrix metalloproteinase-1 (MMP1). Morphological endpoints included potential indicators of placental stress and the extent of cytotrophoblast (CTB)-mediated uterine artery remodeling. Serum PFASs and urinary OPFR metabolites were detected in ∼50%-100% of samples. The most prevalent PFASs were perfluorononanoic acid (PFNA), perfluorooctanoic acid (PFOA), and perfluorooctane sulfonic acid (PFOS), with geometric mean (GM) levels of ∼1.3-2.8 (95% confidence limits from 1.2-3.1) ng/ml compared to ≤0.5 ng/ml for other PFASs. Diphenyl phosphate (DPhP) and bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) were the most prevalent OPFR metabolites, with GMs of 2.9 (95% CI: 2.5-3.4) and 3.6 (95% CI: 2.2-3.1) ng/ml, respectively, compared to <1 ng/ml for bis(2-chloroethyl) phosphate (BCEP) and bis(1-chloro-2-propyl) phosphate (BCIPP). We found inverse associations of PFASs or OPFRs with ITGA1 or CDH5 immunoreactivity and positive associations with indicators of placental stress in multiple basal plate regions, indicating these chemicals may contribute to abnormal placentation and future health risks. Associations with blood pressure and lipid concentrations warrant further examination. This is the first study of these chemicals with placental biomarkers measured directly in human tissues and suggests specific biomarkers are sensitive indicators of exposure during a vulnerable developmental period.
全氟烷基和多氟烷基物质（PFAS）和有机磷酸酯阻燃剂（OPFR）是可能导致胎盘介导的并发症和母婴健康风险的化学物质。很少有研究调查这些化学物质与怀孕期间的效应生物标志物之间的关系。我们在妊娠中期测量了 132 名健康孕妇的 12 种 PFAS 和 4 种尿 OPFR 代谢物，并在亚组中检查了与胎盘发育和疾病相关的生物标志物（n=62）。分子生物标志物包括整合素α-1（ITGA1）、血管内皮钙黏蛋白（CDH5）和基质金属蛋白酶-1（MMP1）。形态学终点包括胎盘应激的潜在指标和滋养层细胞（CTB）介导的子宫动脉重塑的程度。血清 PFAS 和尿 OPFR 代谢物在约 50%-100%的样本中被检测到。最常见的 PFAS 是全氟壬酸（PFNA）、全氟辛酸（PFOA）和全氟辛烷磺酸（PFOS），其几何平均值（GM）水平分别为 1.3-2.8（95%置信区间为 1.2-3.1）ng/ml，而其他 PFAS 的水平则≤0.5ng/ml。二苯基磷酸酯（DPhP）和双（1,3-二氯-2-丙基）磷酸酯（BDCIPP）是最常见的 OPFR 代谢物，其 GM 分别为 2.9（95%CI：2.5-3.4）和 3.6（95%CI：2.2-3.1）ng/ml，而双（2-氯乙基）磷酸酯（BCEP）和双（1-氯-2-丙基）磷酸酯（BCIPP）的水平则<1ng/ml。我们发现 PFAS 或 OPFR 与 ITGA1 或 CDH5 免疫反应呈负相关，与多个基底胎盘区域的胎盘应激标志物呈正相关，这表明这些化学物质可能导致异常胎盘形成和未来的健康风险。与血压和血脂浓度的关联需要进一步研究。这是首次在人体组织中直接测量这些化学物质与胎盘生物标志物的研究，表明特定的生物标志物是易受发育期间暴露影响的敏感指标。
