System chemical biology studies of endocrine disruptors

Endocrine disrupting chemicals (EDCs) alter hormonal balance and other physiological systems through inappropriate developmental or adult exposure, perturbing the reproductive function of further generations. While disruption of key receptors (e.g., estrogen, androgen, and thyroid) at the ligand binding domain (LBD) has been associated with EDCs, a significant number of EDCs do not appear to influence the LBDs of these receptors. Therefore, we evaluated the potential biological effects of EDCs in humans with the aim to rationalize the etiology of certain disorders associated with the reproductive function. We compiled 675 (known or suspected) EDCs and examined chemical-protein associations via ChemProt [http://www.cbs.dtu.dk/services/ChemProt/]. Over 1000 proteins susceptible to perturbation by one or more EDCs were subject to a protein-protein interaction network evaluation. Synergistic EDC effects resulting in the perturbation of different proteins associated to particular diseases (e.g., cryptorchidism) were evaluated.