Background

Prenatal exposure to endocrine-disrupting compounds (EDCs) may contribute to endocrine-related diseases and disorders later in life. Nevertheless, data on in utero exposure to these compounds are still scarce.

Objectives

We investigated a wide range of known and novel nonpolar EDCs in full-term human amniotic fluid (AF), a representative matrix of direct fetal exposure.

Methods

Gas chromatography high-resolution mass spectrometry (GC-HRMS) was used for the targeted and non-targeted analysis of chemicals present in nonpolar AF fractions with dioxin-like, (anti-)androgenic, and (anti-)estrogenic activity. The contribution of detected EDCs to the observed activity was determined based on their relative potencies. The multitude of features detected by non-targeted analysis was tentatively identified through spectra matching and data filtering, and further investigated using curated and freely available sources to predict endocrine activity. Prioritized suspects were purchased and their presence in AF was chemically and biologically confirmed with GC-HRMS and bioassay analysis.

Results

Targeted analysis revealed 42 known EDCs in AF including dioxins and furans, polybrominated diphenyl ethers, pesticides, polychlorinated biphenyls, and polycyclic aromatic hydrocarbons. Only 30% of dioxin activity and <1% estrogenic and (anti-)androgenic activity was explained by the detected compounds. Non-targeted analysis revealed 14,110 features of which 3,243 matched with library spectra. Our data filtering strategy tentatively identified 121 compounds. Further data mining and in silico predictions revealed in total 69 suspected EDCs. We selected 14 chemicals for confirmation, of which 12 were biologically active and 9 were chemically confirmed in AF, including the plasticizer diphenyl isophthalate and industrial chemical p,p'-ditolylamine.

Conclusions

This study reveals the presence of a wide variety of nonpolar EDCs in direct fetal environment and for the first time identifies novel EDCs in human AF. Further assessment of the source and extent of human fetal exposure to these compounds is warranted.

中文翻译：

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人羊水中已知和新型非极性内分泌干扰物的鉴定

背景

产前接触内分泌干扰化合物 (EDC) 可能会导致日后罹患内分泌相关疾病和紊乱。然而，有关子宫内接触这些化合物的数据仍然很少。

目标

我们研究了足月人羊水 (AF) 中的多种已知和新型非极性 EDC，羊水是胎儿直接暴露的代表性基质。

方法

气相色谱高分辨率质谱 (GC-HRMS) 用于对非极性 AF 组分中存在的具有二恶英样、（抗）雄激素和（抗）雌激素活性的化学物质进行靶向和非靶向分析。检测到的 EDC 对观察到的活性的贡献是根据它们的相对效力来确定的。通过光谱匹配和数据过滤初步识别了非靶向分析检测到的众多特征，并使用精心策划的免费来源进行进一步研究以预测内分泌活动。购买优先嫌疑人，并通过 GC-HRMS 和生物测定分析对它们在 AF 中的存在进行化学和生物学证实。

结果

针对性分析揭示了 AF 中 42 种已知的 EDC，包括二恶英和呋喃、多溴二苯醚、农药、多氯联苯和多环芳烃。检测到的化合物仅解释了 30% 的二恶英活性和 <1% 的雌激素和（抗）雄激素活性。非靶向分析揭示了 14,110 个特征，其中 3,243 个与库光谱匹配。我们的数据过滤策略初步识别出 121 种化合物。进一步的数据挖掘和计算机预测揭示了总共 69 种可疑的 EDC。我们选择了 14 种化学品进行确认，其中 12 种具有生物活性，9 种在 AF 中经过化学确认，包括增塑剂间苯二甲酸二苯酯和工业化学品对,对'-二甲苯胺。

结论

这项研究揭示了直接胎儿环境中存在多种非极性 EDC，并首次鉴定了人类 AF 中的新型 EDC。有必要进一步评估人类胎儿接触这些化合物的来源和程度。