Abstract
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. 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. 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. 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. 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.
Highlights
Environmental pollutants are increasingly recognized for their abil ity to alter fetal programming during critical windows of development (Heindel et al, 2015; Vrijheid et al, 2016)
While several thousand man-made substances have been detected to date in the environment, the number of compounds with endocrinedisrupting properties that the fetus might be exposed to is still largely unknown
The workflow used in this study i.e., the combination of tar geted and non-targeted Gas chromatography high-resolution mass spectrometry (GC-HRMS) analysis of amniotic fluid (AF) together with the application of curated and freely available in vitro experimental data and in silico prediction tools, provided a powerful tool to identify known and novel nonpolar endocrine-disrupting compounds (EDCs) in the fetal environment
Summary
Environmental pollutants are increasingly recognized for their abil ity to alter fetal programming during critical windows of development (Heindel et al, 2015; Vrijheid et al, 2016). Lipophilic EDCs are ubiquitously present in the environment with a widespread chronic, low-level exposure in the general population (Bonefeld-Jørgensen et al, 2014; Lee et al, 2006). 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 nontargeted analysis of chemicals present in nonpolar AF fractions with dioxin-like, (anti-)androgenic, and (anti-) estrogenic activity. 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. 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
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
