Neural Mechanisms Underlying the Disruption of Male Courtship Behavior byAdult Exposure to Di(2-ethylhexyl) Phthalate in Mice

International audienceBACKGROUND:Courtship behavior plays a critical role in attracting females and reproduction success. However, the effects of exposure to a ubiqui-tous contaminant di(2-ethylhexyl) phthalate (DEHP) on these behaviors and, in particular, on courtship vocalizations have not been examined.OBJECTIVE:The effects of adult exposure to DEHP on courtship and mating behaviors and gonadotropic axis and neural mechanisms involved inDEHP-induced effects were analyzed in male mice.METHODS:Adult C57BL/6J males were orally exposed to DEHP (0, 0.5, 5, and 50lg=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 testosteronelevels were analyzed. Proteomic and molecular studies were conducted on the hypothalamic preoptic nucleus, the key region involved in sexual moti-vation to vocalize and mate.RESULTS:DEHP at 50lg=kg=d reduced the emission of USVs, whereas lower doses changed the ratio of syllable categories. This was associatedwith diminished sexual interest of female partners toward males exposed to 5 or 50lg=kg=d and increased latency to mate, despite normal olfactorypreference. The kisspeptin system and circulating testosterone levels were unaffected. In DEHP-exposed males, proteomic analysis of the preoptic nu-cleus identified differentially expressed proteins connected to the androgen receptor (AR). Indeed, exposure to 5 or 50lg=kg=d of DEHP inducedselective AR downregulation in this nucleus and upstream chemosensory regions. The involvement of AR changes in the observed alterations was fur-ther supported by the reduced emission of courtship vocalizations in males with disrupted neural AR expression.CONCLUSIONS:These data demonstrate the critical role of neural AR in courtship vocalizations and raises the possibility that the vulnerability of thissignaling pathway to exposure to endocrine disrupters may be detrimental for courtship communication and mating in several species