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Perinatal exposure to octabromodiphenyl ether mixture, DE-79, alters the vasopressinergic system in adult rats.
Toxicology and Applied Pharmacology ( IF 3.3 ) Pub Date : 2020-02-04 , DOI: 10.1016/j.taap.2020.114914
Mhar Y Alvarez-Gonzalez 1 , Eduardo Sánchez-Islas 1 , Samuel Mucio-Ramirez 1 , Patricia de Gortari 2 , María I Amaya 2 , Prasada Rao S Kodavanti 3 , Martha León-Olea 1
Affiliation  

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.

中文翻译:

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能系统。

多溴二苯醚(PBDEs)是持久性环境污染物,被视为神经毒剂和内分泌干扰物,具有重要的生物学作用,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(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。但是,尚不清楚含八溴二苯醚化合物的混合物(如DE-79)对AVPergic系统的潜在不利影响。本研究旨在检查围产期DE-79暴露对AVPergic系统的影响。从妊娠第6天到出生后第21天,按0(对照),1.7(低)或10.2(高)mg / kg /天的剂量给药水坝,在3个月大时,所有剂量的雄性和雄性后代均受到常渗和高渗攻击。雄性后代随后评估渗透调节的改变(即血清渗透压和全身性加压素释放),以及下丘脑室旁和视上核中加压素的免疫反应性(AVP-IR)和基因表达。另外,为了阐明DE-79对AVPergic系统的影响的可能机制,在同一下丘脑核中研究了神经元一氧化氮合酶免疫反应性(nNOS-IR)和mRNA表达。结果表明,成年期在正常条件下,以及在高渗刺激下,围产期DE-79暴露的AVP-1R,mRNA表达和全身释放更为明显。在同一细胞核中,nNOS-1R和mRNA表达也受到影响。
更新日期:2020-02-04
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