Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts, USA.
Environ Health Perspect. 2010 Feb;118(2):291-6. doi: 10.1289/ehp.0900788.
Phthalates can alter steroidogenesis and peroxisome proliferator-activated receptor gamma (PPARgamma)mediated transcription in rodent tissues. The placenta offers a rich source of biomarkers to study these relationships in humans.
We evaluated whether gestational phthalate exposures in humans were associated with altered human placental steroidogenesis and trophoblast differentiation as measured by markers of mRNA transcription.
We measured seven target genes in placentas collected from 54 Dominican and African-American women at delivery in New York City using quantitative real-time polymerase chain reaction (qPCR), normalized to 18S rRNA. qPCR results for the target genes were log-transformed, converted to Z-scores, and grouped into two functional pathways: steroidogenesis (aromatase, cholesterol side chain cleavage enzyme, 17beta-hydroxysteroid dehydrogenase type 1, and cytochrome P450 1B1) and trophoblast differentiation (PPARgamma, aryl hydrocarbon receptor, and human chorionic gonadotropin). Repeated measures models were used to evaluate the association of phthalate metabolites measured in third-trimester urine samples with each group of target genes, accounting for correlation among the genes within a pathway.
Higher urinary concentrations of five phthalate metabolites were associated with lower expression of the target genes reflecting trophoblast differentiation. Results were less consistent for genes in the steroidogenesis pathway and suggested a nonlinear dose-response pattern for some phthalate metabolites.
We observed a significant association between prenatal exposure to phthalates and placental gene expression within two pathways. Further studies are warranted to understand the significance of this association with respect to fetal development and placental function.
邻苯二甲酸酯可改变啮齿动物组织中的类固醇生成和过氧化物酶体增殖物激活受体γ（PPARγ）介导的转录。胎盘为研究人类中这些关系提供了丰富的生物标志物来源。
我们评估了人类妊娠期间邻苯二甲酸酯暴露是否与改变的人类胎盘类固醇生成和滋养层分化有关，这些改变通过 mRNA 转录标志物来衡量。
我们使用定量实时聚合酶链反应（qPCR）测量了来自 54 名多米尼加和非裔美国妇女在纽约市分娩时胎盘的七个靶基因，并用 18S rRNA 进行标准化。将靶基因的 qPCR 结果进行对数转换，转换为 Z 分数，并分为两个功能途径：类固醇生成（芳香酶、胆固醇侧链裂解酶、17β-羟类固醇脱氢酶 1 型和细胞色素 P450 1B1）和滋养层分化（PPARγ、芳烃受体和人绒毛膜促性腺激素）。使用重复测量模型评估第三孕期尿液样本中测量的邻苯二甲酸代谢物与每个靶基因组的关联，同时考虑了途径内基因之间的相关性。
五种邻苯二甲酸代谢物的尿液浓度较高与反映滋养层分化的靶基因表达降低有关。类固醇生成途径中的基因结果不太一致，并提示某些邻苯二甲酸代谢物存在非线性剂量反应模式。
我们观察到产前暴露于邻苯二甲酸酯与两种途径中的胎盘基因表达之间存在显著关联。需要进一步研究以了解这种与胎儿发育和胎盘功能的关联的意义。
