Integrated metabolomic, lipidomic and steroidomic profiling for revealing signatures and markers of effect induced by bisphenols exposure on human testicular function
Résumé
The Newplast research project (ANR-13-CESA-0012-01) focuses on substitutes and derivatives of bisphenol A (BPA) which are used in the manufacture of polycarbonate and epoxy resins, including food contact materials. Its global objective is to generate data and knowledge as regards (i) their biotransformation and biological impact on the human hepatic and reproductive functions, (ii) their modes of actions at molecular level through ligand-receptor binding / transactivation mechanisms and (iii) human external and internal exposure assessment. The effect of BPA and related substitutes (BPS and BPF) on testicular function was assessed on fetal (FEGA) and adult (TEXAS) models using an integrated metabolomic, lipidomic and steroidomic profiling approach. Three complementary workflows were then combined to generate a unique set of biological signatures as a support for markers of effect discovery. A rationalized sample preparation permitted to fractionate each characterized sample into one polar fraction for RPLC-ESI(+/-)-HRMS metabolomic profiling, and one apolar phase for RPLC-ESI(+/-)-HRMS lipidomic and GC-EI-MS/MS steroidomic profiling. Moreover a comprehensive characterization from both culture medium (exo-metabolome) and testicular tissue (endo-metabolome) was achieved. All together, obtained results give an extended picture of biological disruptions induced by BPA and two main substitutes (BPS and BPF) on human testicular target, including dose-responses and mixture effects. A set of annotated and particularly affected metabolites was revealed from each investigated metabolome sub-component.
Domaines
Chimie analytiqueOrigine | Fichiers produits par l'(les) auteur(s) |
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