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内分泌干扰物 DE-79 改变雄性大鼠的催产素能传递和性行为表达。

The endocrine disruptor DE-79 alters oxytocinergic transmission and sexual behavior expression in male rats.

机构信息

Departamento de Farmacobiología, Cinvestav Sede Sur, Calzada de los Tenorios 235, Col. Granjas Coapa, Delegación Tlalpan, Ciudad de México C.P.14330, Mexico.

Departamento de Farmacobiología, Cinvestav Sede Sur, Calzada de los Tenorios 235, Col. Granjas Coapa, Delegación Tlalpan, Ciudad de México C.P.14330, Mexico.

出版信息

Toxicol Appl Pharmacol. 2023 Nov 15;479:116723. doi: 10.1016/j.taap.2023.116723. Epub 2023 Oct 14.

Abstract

Polybrominated diphenyl ethers (PBDEs), used as flame retardants are persistent organic pollutants exerting important health effects. PBDEs with >5 bromide substitutions were considered less harmful and therefore extensively used commercially. DE-79 was a widely used PBDE mixture of hexa-, hepta-, octa- and nona-brominated compounds that increases vasopressin (AVP) production. AVP and oxytocin (OT) are both produced in neurons of the supraoptic (SON) and paraventricular (PVN) hypothalamic nuclei projecting to the neurohypophysis and to brain regions involved in copulatory behavior. OT plays an important role in male copulation. Since DE-79 alters AVP expression in the SON and PVN, it might also modify OT content and alter male sexual behavior. We analyzed if repeated DE-79 exposure of adult male rats affected OT content and OT receptor (OTR) density in the SON, PVN, medial preoptic area (mPOA), ventral tegmental area, nucleus accumbens, and amygdala, and if male copulatory behavior was affected. We show that DE-79 exposure produces a generalized decrease in brain OT immunoreactivity, increases OTR density in all brain regions analyzed but the mPOA, and reduces the ejaculatory threshold after a first ejaculation. The documented ejaculation-induced OT release might participate in this last effect. Thus, one-week DE-79 exposure alters the OT-OTR system and modifies male rat sexual performance. Based on the literature it could be speculated that these effects are related to the putative endocrine disrupting actions of DE-79, ultimately altering brain OT levels and OTR expression that might affect copulation and other important OT-mediated brain functions.

摘要

多溴联苯醚(PBDEs)作为阻燃剂是持久性有机污染物,对健康有重要影响。具有 >5 个溴取代基的 PBDEs 被认为危害较小,因此被广泛用于商业用途。DE-79 是一种广泛使用的 PBDE 混合物,由六溴、七溴、八溴和九溴化合物组成,可增加血管加压素(AVP)的产生。AVP 和催产素(OT)均由下丘脑视上核(SON)和室旁核(PVN)神经元产生,投射到神经垂体,并投射到参与交配行为的脑区。OT 在雄性交配中起着重要作用。由于 DE-79 改变了 SON 和 PVN 中的 AVP 表达,它也可能改变 OT 含量并改变雄性性行为。我们分析了成年雄性大鼠反复暴露于 DE-79 是否会影响 SON、PVN、中脑视前区(mPOA)、腹侧被盖区、伏隔核和杏仁核中的 OT 含量和 OT 受体(OTR)密度,以及是否会影响雄性交配行为。我们发现,DE-79 暴露会导致大脑 OT 免疫反应普遍减少,增加所有分析脑区的 OTR 密度,但 mPOA 除外,并降低首次射精后的射精阈值。记录到的射精诱导的 OT 释放可能参与了最后这一效应。因此,一周的 DE-79 暴露会改变 OT-OTR 系统,并改变雄性大鼠的性表现。根据文献,我们可以推测这些影响与 DE-79 的潜在内分泌干扰作用有关,最终改变大脑 OT 水平和 OTR 表达,从而影响交配和其他重要的 OT 介导的大脑功能。

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