Dataset Information

Method Development for Effect-Directed Analysis of Endocrine Disrupting Compounds in Human Amniotic Fluid.

ABSTRACT: The developing fetus represents a highly sensitive period of exposure to endocrine disrupting compounds (EDCs). However, risk assessment of EDCs is hampered by the lack of data on direct in utero exposure. In this study, we developed a robust analytical methodology for the identification of a wide range of known and unknown EDCs in full-term amniotic fluid (AF). First, a method for extraction and fractionation of a broad range of polar and nonpolar EDCs was developed and validated. Maximal recoveries of reference compounds and minimal interference from the matrix were achieved with a combination of solid phase extraction and dispersive liquid/liquid extraction. Bioassay analysis using cell-based reporter gene assays revealed estrogenic, androgenic, and dioxin-like activity in AF extract corresponding to 1.4 nmol EEQ/L, 76.6 pmol DHT-EQ/L, and 10.1 pmol TEQ/L, respectively. Targeted analysis revealed 13 xenobiotics, phytoestrogens, and endogenous hormones in the AF extract that partly contributed to the bioassay activity. Separation of the complex mixture of chemicals in the AF extract with reversed-phase chromatographic fractionation and subsequent bioassay analysis revealed activity in fractions over a wide range of polarity, indicating diverse (unidentified) substances with potential ED activity. The method developed here represents the first methodological step in an effect-directed analysis approach to identify unknown biologically active compounds in the fetal environment.

SUBMITTER: Dusza HM

PROVIDER: S-EPMC6921688 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Method Development for Effect-Directed Analysis of Endocrine Disrupting Compounds in Human Amniotic Fluid.

Dusza Hanna M HM Janssen Elwin E Kanda Rakesh R Legler Juliette J

Environmental science & technology 20191021 24

The developing fetus represents a highly sensitive period of exposure to endocrine disrupting compounds (EDCs). However, risk assessment of EDCs is hampered by the lack of data on direct in utero exposure. In this study, we developed a robust analytical methodology for the identification of a wide range of known and unknown EDCs in full-term amniotic fluid (AF). First, a method for extraction and fractionation of a broad range of polar and nonpolar EDCs was developed and validated. Maximal recov ...[more]

PMID: 31584268

Similar Datasets

Project description:BackgroundEvidence has indicated that some non-inherited factors such as exposure to environmental pollutants are associated with neurodevelopment disorders like autism spectrum disorder (ASD). Studies report that endocrine disrupting compounds (EDCs), including polychlorinated biphenyls, organochlorine pesticides, perfluoroalkyl substances (PFAS), and some metals, have adverse effects on the fetal neurodevelopment. The aim of this study was to measure the amniotic fluid (AF) levels of EDCs and metals as well as the receptor transactivities induced by AF and investigate the possible link between prenatal exposure to EDCs and heavy metals and ASD risk.MethodsIn this case-control study, we included AF samples of 75 ASD cases and 135 frequency-matched controls and measured the levels of the endogenous sex hormones, PFAS, and elements including heavy metals. The combined effect of endogenous hormones and EDCs on the receptor of estrogen (ER), androgen (AR), aryl hydrocarbon (AhR), and thyroid hormone-like activity were also determined and expressed as receptor ligand equivalents. We assessed the associations of AF levels of chemicals, sex hormones, and receptor activities with ASD risk using unconditional logistical regression analyses. To control for multiple comparisons, the false discovery rate (FDR) was used and q values less than 0.25 were designated as statistical significance.ResultsPFAS and metals were detectable in AF samples. The ASD cases had significantly lower AF levels of PFAS than controls, and the adjusted odds ratio (OR) was 0.410 (95% CI 0.174, 0.967; p?=?0.042; FDR q value?=?0.437) for perfluorooctane sulfonate (PFOS). The principal component, including PFAS congeners, copper, iron, and estrogenic activity, was significantly inversely associated with ASD risk (adjusted OR?=?0.100; 95% CI 0.016, 0.630; p?=?0.014; FDR q value?=?0.098).Testosterone level in AF weakly associated with ASD risk (adjusted OR?=?1.002; 95% CI 1.000, 1.004; p?=?0.05). However, after multiple comparison correction, the association was not significant (FDR q value?=?0.437). No significant associations between AF-induced receptor transactivities and ASD risk were observed. The adjusted OR was 2.176 (95%CI 0.115, 41.153) for the ratio of the combined androgenic activity to combined estrogenic activity.ConclusionsThe presence of PFAS and heavy metals in AF indicates that they can cross the placenta. The inverse association between levels of PFAS congeners in AF and ASD risk might relate to the weak estrogenic activities and anti-androgenic activities of PFAS.The observed tendency of positive association between the ratio of combined androgenic effect to the combined estrogenic effect and ASD risk needs further studies to explore whether EDCs together with endogenous hormones play a role in the development of ASD.

Dataset Information

Method Development for Effect-Directed Analysis of Endocrine Disrupting Compounds in Human Amniotic Fluid.

Publications

Method Development for Effect-Directed Analysis of Endocrine Disrupting Compounds in Human Amniotic Fluid.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets