Thyroid Hormone-Disrupting Potentials of Major Benzophenones in Two Cell Lines (GH3 and FRTL-5) and Embryo-Larval Zebrafish

Abstract

Benzophenones (BPs) have been widely used in personal care products (PCPs) such as UV protectants. Sex endocrine-disrupting effects have been documented for some BPs, but, significant knowledge gaps are present for their thyroid-disrupting effects. To investigate the thyroid-disrupting potential of BPs, a rat pituitary (GH3) and thyroid follicle (FRTL-5) cell line were employed on six BPs, i.e., benzophenone (BP), benzophenone-1 (BP-1), benzophenone-2 (BP-2), benzophenone-3 (BP-3), benzophenone-4 (BP-4), and benzophenone-8 (BP-8). Subsequently, zebrafish (Danio rerio) embryo exposure was conducted for three potent BPs that were identified based on the transcriptional changes observed in the cells. In GH3 cells, all BPs except BP-4 down-regulated the Tsh beta, Trhr, and Tr beta genes. In addition, some BPs significantly up-regulated the Nis and Tg genes while down-regulating the Tpo gene in FRTL-5 cells. In zebrafish embryo assay conducted for BP-1, BP-3, and BP-8, significant decreases in whole-body T4 and T3 level were observed at 6 day postfertilization (dpf). The up-regulation of the dio I and ugtlab genes in the fish suggests that decreased thyroid hormones are caused by changing metabolism of the hormones. Our results show that these frequently used BPs can alter thyroid hormone balances by influencing the central regulation and metabolism of the hormones.