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围产期暴露于八溴二苯醚混合物 DE-79 会改变成年大鼠的血管加压素能系统。

Perinatal exposure to octabromodiphenyl ether mixture, DE-79, alters the vasopressinergic system in adult rats.

机构信息

Departamento de Neuromorfología Funcional, Dirección de Investigaciones en Neurociencias, Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz, Calz. México Xochimilco No. 101, Col. San Lorenzo Huipulco, Ciudad de México, C.P. 14370, Mexico.

Laboratorio de Neurofisiología Molecular, Dirección de Investigaciones en Neurociencias, Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz, Calz. México Xochimilco No. 101, Col. San Lorenzo Huipulco, Ciudad de México, C.P. 14370, Mexico.

出版信息

Toxicol Appl Pharmacol. 2020 Mar 15;391:114914. doi: 10.1016/j.taap.2020.114914. Epub 2020 Feb 4.

Abstract

Polybrominated diphenyl ethers (PBDEs) are persistent environmental pollutants considered as neurotoxicants and endocrine disruptors with important biological effects ranging from alterations in growth, reproduction, and effects on the hypothalamus-pituitary-adrenal axis. The vasopressinergic (AVPergic) system is a known target for pentaBDEs mixture (DE-71) and the structurally similar chemicals, polychlorinated biphenyls. However, the potential adverse effects of mixtures containing octaBDE compounds, like DE-79, on the AVPergic system are still unknown. The present study aims to examine the effects of perinatal DE-79 exposure on the AVPergic system. Dams were dosed from gestational day 6 to postnatal day 21 at doses of 0 (control), 1.7 (low) or 10.2 (high) mg/kg/day, and male offspring from all doses at 3-months-old were subjected to normosmotic and hyperosmotic challenge. Male offspring where later assessed for alterations in osmoregulation (i.e. serum osmolality and systemic vasopressin release), and both vasopressin immunoreactivity (AVP-IR) and gene expression in the hypothalamic paraventricular and supraoptic nuclei. Additionally, to elucidate a possible mechanism for the effects of DE-79 on the AVPergic system, both neuronal nitric oxide synthase immunoreactivity (nNOS-IR) and mRNA expression were investigated in the same hypothalamic nuclei. The results showed that perinatal DE-79 exposure AVP-IR, mRNA expression and systemic release in adulthood under normosmotic conditions and more evidently under hyperosmotic stimulation. nNOS-IR and mRNA expression were also affected in the same nuclei. Since NO is an AVP regulator, we propose that disturbances in NO could be a mechanism underlying the AVPergic system disruption following perinatal DE-79 exposure leading to osmoregulation deficits.

摘要

多溴联苯醚(PBDEs)是持久性环境污染物,被认为具有神经毒性和内分泌干扰作用,具有广泛的生物学效应,包括生长、繁殖的改变以及对下丘脑-垂体-肾上腺轴的影响。血管加压素能(AVPergic)系统是五溴二苯醚混合物(DE-71)和结构相似的化学物质多氯联苯的已知靶标。然而,含有八溴二苯醚化合物(如 DE-79)的混合物对 AVPergic 系统的潜在不良影响尚不清楚。本研究旨在研究围产期 DE-79 暴露对 AVPergic 系统的影响。从妊娠第 6 天到产后第 21 天,母鼠每天以 0(对照)、1.7(低)或 10.2(高)mg/kg 的剂量给药,所有剂量的雄性后代在 3 个月大时进行等渗和高渗挑战。雄性后代随后评估渗透调节的变化(即血清渗透压和全身血管加压素释放),以及下丘脑室旁核和视上核的血管加压素免疫反应性(AVP-IR)和基因表达。此外,为了阐明 DE-79 对 AVPergic 系统影响的可能机制,还研究了同一下丘脑核中的神经元型一氧化氮合酶免疫反应性(nNOS-IR)和 mRNA 表达。结果表明,围产期 DE-79 暴露会导致成年后 AVP-IR、mRNA 表达和全身释放,在等渗条件下更为明显,在高渗刺激下更为明显。同一核中的 nNOS-IR 和 mRNA 表达也受到影响。由于 NO 是 AVP 的调节剂,我们提出,NO 的紊乱可能是围产期 DE-79 暴露后 AVPergic 系统紊乱导致渗透调节缺陷的机制之一。

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Epigenetic Effects of Polybrominated Diphenyl Ethers on Human Health.多溴联苯醚对人类健康的表观遗传效应。
Int J Environ Res Public Health. 2019 Jul 29;16(15):2703. doi: 10.3390/ijerph16152703.

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