Involvement of estrogen receptor alpha (ERα) and impairment of steroidogenesis after exposure to tris(2,3-dibromopropyl) isocyanurate (TBC) in mouse spermatogenic (GC-1 spg) cells in vitro

体外小鼠生精细胞 (GC-1 spg) 暴露于三(2,3-二溴丙基)异氰尿酸酯 (TBC) 后雌激素受体 α (ERα) 的参与和类固醇生成的受损

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作者:Anna Tabęcka-Łonczyńska, Piotr Kaczka, Edyta Kaleniuk

Abstract

Good-quality reproductive cells are essential for reproduction. Endocrine disruptors are widely available in the environment and are known to have an adverse effect on spermatogenesis and steroidogenesis. One of them is tris(2,3-dibromopropyl) isocyanurate (TBC), i.e. one of the novel brominated flame retardants (NBFR). TBC is a widely distributed ingredient used in the production of flame retardants. Currently, it is known to affect the hormonal system, but the exact mechanism of its action is unknown. Therefore, the aim of the study was to determine whether TBC alone and in cotreatment with BHPI (estrogen receptor alpha antagonist) has an impact on the expression of nuclear receptors involved in the formation of steroid hormones, proteins, and enzymes responsible for steroidogenesis and the levels of steroid hormones (E2, P4, and T) in the GC-1 spg cell line as a mouse model of spermatogenic cells in vitro. Our results indicate that ERα is involved in the mechanism of TBC action, while no activation of PPARγ, AhR, and IGF-1R was observed. In addition, a decrease in the levels of most of the analyzed proteins and enzymes involved in steroid conversion was observed. Only Cyp19a1 was upregulated after TBC, BHPI, and TBC with BHPI cotreatment. In all the analyzed groups, a significant decrease in P4 and a subtle decrease in T and E2 were observed in the production and secretion of the hormones to the culture medium, compared to the control. The obtained results confirm the involvement of TBC in the dysregulation of steroid biosynthesis, which may affect male fertility.

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