Structural binding interactions of tetrabromobisphenol A with sex steroid nuclear receptors and sex hormone-binding globulin.

Tetrabromobisphenol A (TBBPA) is a widely used brominated flame retardant owing to its efficient fire-breaking property. However, leaching of TBBPA into the environment has been a global health concern due to the endocrine-disrupting activity (EDA) associated with TBBPA exposure. Limited studies are available on the hazardous effects of TBBPA on reproductive function. The aim of the present study was the structural characterization of potential EDA of TBBPA in reproductive hormone signaling and transport including steroid nuclear receptors, such as estrogen receptor alpha (ERα), estrogen receptor beta (ERβ), androgen receptor (AR), progesterone receptor (PR), and the steroid transport protein, sex hormone-binding globulin (SHBG). The structural binding characterization of TBBPA with the sex steroid nuclear receptors and transport protein was performed by induced-fit docking using the Schrödinger 2017 suite. The results revealed that the TBBPA binding pattern and molecular interactions with the indicated receptors and transport protein displayed overall similarity with their respective native ligands. The estimated binding energy value of TBBPA for ERα was similar to the native ligand, estradiol, indicating tight binding and greater potential for TBBPA to disrupt ERα signaling. For ERβ, AR, PR and SHBG, the estimated binding energy values were also close to their respective native ligands, indicating potential for interference in native hormone signaling and transport. In conclusion, TBBPA exposure in humans may potentially cause disruption of sex steroid signaling and transport, and thus lead to reproductive dysfunction.