Dombret Carlos, Capela Daphné, Poissenot Kevin, Parmentier Caroline, Bergsten Emma, Pionneau Cédric, Chardonnet Solenne, Hardin-Pouzet Hélène, Grange-Messent Valérie, Keller Matthieu, Franceschini Isabelle, Mhaouty-Kodja Sakina
Sorbonne Universités, UPMC Univ Paris 06, INSERM, CNRS , Neuroscience Paris Seine - Institut de Biologie Paris Seine, Paris, France.
Institut National de la Recherche Agronomique, Unité Mixte de Recherche 85 , Nouzilly, France.
Environ Health Perspect. 2017 Sep 1;125(9):097001. doi: 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 50μg/kg/d) 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 50μg/kg/d 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 50μg/kg/d 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 50μg/kg/d 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.
求偶行为在吸引雌性和繁殖成功方面起着关键作用。然而，暴露于一种普遍存在的污染物邻苯二甲酸二（2-乙基己基）酯（DEHP）对这些行为，特别是对求偶叫声的影响尚未得到研究。
分析成年雄性小鼠暴露于DEHP对求偶和交配行为、促性腺轴以及DEHP诱导效应所涉及的神经机制的影响。
成年C57BL/6J雄性小鼠经口暴露于DEHP（0、0.5、5和50μg/kg/d）4周。测量嗅觉偏好、超声波发声（USV）、伴侣偏好和交配情况，以及运动活性和运动协调性。分析促性腺激素释放激素神经元系统和睾酮水平。对下丘脑视前核进行蛋白质组学和分子研究，该区域是参与发声和交配性动机的关键区域。
50μg/kg/d的DEHP降低了USV的发出，而较低剂量改变了音节类别比例。这与暴露于5或50μg/kg/d的雄性小鼠对雌性伴侣的性兴趣降低以及交配潜伏期延长有关，尽管嗅觉偏好正常。促性腺激素释放激素神经元系统和循环睾酮水平未受影响。在暴露于DEHP的雄性小鼠中，视前核的蛋白质组学分析鉴定出与雄激素受体（AR）相关的差异表达蛋白。事实上，暴露于5或50μg/kg/d的DEHP诱导该核及上游化学感觉区域的AR选择性下调。神经AR表达受损的雄性小鼠求偶叫声发出减少，进一步支持了AR变化参与观察到的改变。
这些数据证明了神经AR在求偶叫声中的关键作用，并提出这种信号通路易受内分泌干扰物影响的可能性可能对多个物种的求偶交流和交配有害。https://doi.org/10.1289/EHP1443
