Endocrine-disrupting potential of polybrominated diphenyl ethers (PBDEs) on androgen receptor signaling: a structural insight

Polybrominated diphenyl ethers (PBDEs) are commonly used in array of consumer items to improve their fire-resisting ability. The PBDE compounds are non-covalently linked with substrate polymer matrices resulting in their consistent leach out and ubiquitous presence in the environment. Increasing evidence of PBDEs having endocrine-disrupting effects perturbing the homeostasis of sex hormones and causing adverse effects on reproductive system has been shown. The two frequently reported PBDE congeners from human samples are 2,2′,4,4′-tetra-bromodiphenyl ether (BDE-47) and 2,2′,4,4′,5-penta-bromodiphenyl ether (BDE-99). The focus of the present study was to investigate the potential disruptive action of BDE-47 and BDE-99 and their hydroxy (HO-) and methoxy (MeO-) structural analogues on androgen receptor (AR). The structural binding characterization of these ligands against AR was accomplished following the induced fit docking and binding energy estimations. The results revealed that the indicated compounds are packed tightly in the AR ligand-binding pocket, displaying similar binding pattern to the native-ligand testosterone. The MeO- structural analogues of both the PBDEs showed higher binding energy values than their HO- counterparts with 6-MeO-BDE-99 having binding energy values similar to testosterone and highest among all the ligands in this study. In conclusion, the results of this study suggested potential disruptive action of BDE-47 and BDE-99 and their analogues particularly for 6-MeO-BDE-99 on AR signaling pathway, which may adversely impact the male reproductive growth and function.