Neural Mechanisms Underlying the Disruption of Male Courtship Behavior by Adult Exposure to Di(2-ethylhexyl) Phthalate in Mice.
Neural Mechanisms Underlying the Disruption of Male Courtship Behavior by Adult Exposure to Di(2-ethylhexyl) Phthalate in Mice.
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DOI：
10.1289/ehp1443
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发表时间：
2017-09-01
影响因子：
10.4
通讯作者：
Mhaouty-Kodja S
中科院分区：
文献类型：
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作者：
Dombret C;Capela D;Poissenot K;Parmentier C;Bergsten E;Pionneau C;Chardonnet S;Hardin-Pouzet H;Grange-Messent V;Keller M;Franceschini I;Mhaouty-Kodja S
求偶行为在吸引雌性和繁殖成功方面起着至关重要的作用。然而，暴露在无处不在的污染物邻苯二甲酸二(2-乙基己基)酯(DEHP)中对这些行为的影响，特别是对求偶发声的影响还没有被研究过。分析了成年小鼠暴露于DEHP对雄性小鼠的求偶行为和交配行为的影响，以及与DEHP诱导效应有关的促性腺轴和神经机制。成年C57BL/6J雄性小鼠口服DEHP(0、0.5、5和)4wk。测量嗅觉偏好、超声发声(USV)、伴侣偏好和交配，以及运动活动和运动协调。分析Kispeptin系统和睾酮水平。对下丘脑视前核进行了蛋白质组学和分子研究，这是涉及发声和交配的性动机的关键区域。低剂量的DEHP可减少USVs的发射，但改变音节类别的比例。这与女性伴侣对暴露于5或5或的男性的性兴趣减弱和交配潜伏期延长有关，尽管嗅觉偏好正常。Kispeptin系统和循环中的睾酮水平没有受到影响。在接触DEHP的男性中，对视前核的蛋白质组学分析发现了与雄激素受体(AR)相关的差异表达蛋白质。事实上，暴露于5或DEHP可诱导该核团和上游化学感受区AR的选择性下调。AR神经表达中断的男性求偶发声的减少进一步支持了AR变化与观察到的变化的关系。这些数据证明了神经AR在求偶发声中的关键作用，并提出了这一信号通路暴露于内分泌干扰物的脆弱性可能对几个物种的求偶、交流和交配不利的可能性。Https://doi.org/10.1289/EHP1443
Courtship behavior plays a critical role in attracting females and reproduction success. However, the effects of exposure to a ubiquitous contaminant di(2-ethylhexyl) phthalate (DEHP) on these behaviors and, in particular, on courtship vocalizations have not been examined. The effects of adult exposure to DEHP on courtship and mating behaviors and gonadotropic axis and neural mechanisms involved in DEHP-induced effects were analyzed in male mice. Adult C57BL/6J males were orally exposed to DEHP (0, 0.5, 5, and ) for 4 wk. Olfactory preference, ultrasonic vocalizations (USVs), partner preference and mating, as well as locomotor activity and motor coordination, were measured. The kisspeptin system and testosterone levels were analyzed. Proteomic and molecular studies were conducted on the hypothalamic preoptic nucleus, the key region involved in sexual motivation to vocalize and mate. DEHP at reduced the emission of USVs, whereas lower doses changed the ratio of syllable categories. This was associated with diminished sexual interest of female partners toward males exposed to 5 or and increased latency to mate, despite normal olfactory preference. The kisspeptin system and circulating testosterone levels were unaffected. In DEHP-exposed males, proteomic analysis of the preoptic nucleus identified differentially expressed proteins connected to the androgen receptor (AR). Indeed, exposure to 5 or of DEHP induced selective AR downregulation in this nucleus and upstream chemosensory regions. The involvement of AR changes in the observed alterations was further supported by the reduced emission of courtship vocalizations in males with disrupted neural AR expression. These data demonstrate the critical role of neural AR in courtship vocalizations and raises the possibility that the vulnerability of this signaling pathway to exposure to endocrine disrupters may be detrimental for courtship communication and mating in several species. https://doi.org/10.1289/EHP1443