Background

Human fetal exposures to polybrominated diphenyl ethers (PBDEs) and their metabolites (OH-PBDEs) are unique from adults, and in combination with a different metabolic profile, may make fetal development more sensitive to adverse health outcomes from these exposures. However, we lack data to characterize human fetal PBDE exposures and the metabolic factors that can influence these exposures.

Objective

We examined differences between 2nd trimester maternal and fetal exposures to PBDEs and OH-PBDEs. We also characterized fetal cytochrome P450 (CYP) mRNA expression and its associations with PBDE exposures.

Methods

We collected paired samples of maternal serum and fetal liver (n = 86) with a subset having matched placenta (n = 50). We measured PBDEs, OH-PBDEs, and mRNA expression of CYP genes (e.g. CYP1A1, -2E1, -2J2, -2C9) in all samples. As a sensitivity analysis, we measured PBDEs and OH-PBDEs in umbilical cord serum from a subset (n = 22).

Results

BDE-47 was detected in ≥ 96% of all tissues. Unadjusted ∑PBDEs concentrations were highest in fetal liver (geometric mean (GM) = 0.72 ng/g), whereas lipid-adjusted concentrations were highest in cord serum (111.12 ng/g lipid). In both cases, fetal concentrations were approximately two times higher than maternal serum levels (GM = 0.33 ng/g or 48.75 ng/g lipid). ΣOH-PBDEs were highest in maternal and cord sera and 20–200 times lower than PBDE concentrations. In regression models, maternal BDE-47 explained more of the model variance of liver than of placenta BDE-47 concentrations (adjusted R² = 0.79 vs 0.48, respectively). In adjusted logistic regression models, ∑PBDEs were positively associated with expression of CYP2E1 and -2J2 (placenta), and -1A1 (liver) (p < 0.05).

Conclusion

Our findings suggest that under normal conditions of mid-gestation, the human fetus is directly exposed to concentrations of PBDEs that may be higher than previously estimated based on maternal serum and that these exposures are associated with the expression of mRNAs coding for CYP enzymes. These results will help frame and interpret findings from studies that use maternal or cord blood as proxy measures of fetal exposures, and will inform the molecular pathways by which PBDEs affect human health.

中文翻译：

---

母体和胎儿组织中的多溴联苯醚（PBDEs）和羟基化PBDE代谢物（OH-PBDEs），以及与胎儿细胞色素P450基因表达的关联

背景

人类胎儿暴露于多溴二苯醚（PBDEs）及其代谢产物（OH-PBDEs）是成年人所独有的，结合不同的代谢特征，可能会使胎儿发育对这些暴露对健康的不良后果更加敏感。但是，我们缺乏表征人类胎儿PBDE暴露以及可能影响这些暴露的代谢因子的数据。

客观的

我们检查了孕中期和孕期胎儿和母婴接触多溴二苯醚和OH-PBDEs的差异。我们还表征了胎儿细胞色素P450（CYP）mRNA的表达及其与PBDE暴露的关系。

方法

我们收集了母体血清和胎儿肝脏（n  = 86）的配对样本，其中子集具有匹配的胎盘（n  = 50）。我们测量了所有样品中的PBDEs，OH-PBDEs和CYP基因的mRNA表达（例如CYP1A1，-2E1，-2J2，-2C9）。作为敏感性分析，我们从一个子集（n  = 22）中测量了脐带血清中的PBDEs和OH-PBDEs 。

结果

在所有组织的≥96％中检测到BDE-47。胎肝中未经调整的∑PBDEs浓度最高（几何平均值（GM）= 0.72 ng / g），而脐带血清中经脂质调整的浓度最高（111.12 ng / g脂质）。在这两种情况下，胎儿浓度都比母体血清水平高约两倍（GM = 0.33 ng / g或48.75 ng / g脂质）。ΣOH-PBDEs在母体和脐带血清中最高，比PBDE浓度低20-200倍。在回归模型中，孕妇的BDE-47解释的肝脏模型差异大于胎盘BDE-47的浓度（经调整的R ² 分别为0.79和0.48）。在调整后的逻辑回归模型中，∑PBDEs与CYP2E1和-2J2（胎盘）和-1A1（肝脏）的表达呈正相关（p  <0.05）。

结论

我们的发现表明，在妊娠中期的正常条件下，人类胎儿直接暴露于可能高于先前基于母体血清估计的PBDEs浓度，并且这些暴露与编码CYP酶的mRNA的表达有关。这些结果将有助于框架化和解释使用母血或脐带血作为胎儿暴露指标的研究结果，并将为多溴二苯醚影响人类健康的分子途径提供信息。