Sexual behavior in male mice is impaired by an obesogenic-diabetogenic diet and worsened by exposure to a relevant environmental mixture of phthalates

The decrease in male fertility observed since the beginning of the 20^th century in Western countries could be linked to changes in diets and exposure to molecules from industry, such as endocrine disruptors (ED) and among them, phthalates. Despite those lifestyle changes, the combined effect of adult exposure to environmentally relevant doses of phthalates and obesity has never been explored. Thus, we evaluated the combined effects of a high fat/high fructose diet (HFHF) and exposure to an environmental mixture of phthalates (mix) on male murine sexual behavior. Four groups of adult male C57Bl/6J mice were exposed during 17 weeks to a control diet (CD), a control diet coupled with the mix (CDmix), an HFHF diet, and an HFHF diet coupled with the mix (HFHFmix). Both HFHF and HFHFmix diets induced metabolic alterations. The HFHFmix diet altered the efficiency of sexual behavior, with a dramatic decrease in the number of animals reaching ejaculation. HFHFmix effect was associated with a loss in discrimination toward female counterparts in an olfactory preference test. The effect of the HFHFmix on the cellular and molecular markers of the preoptic area of the hypothalamus (mPOA), the main integrating center in the control of male sexual behavior, demonstrated an alteration in the neural network. Thus, the synergistic effect of an HFHF diet and exposure to phthalates, at doses relevant for human exposure, on male sexual behavior, revealed a specific vulnerability of the central nervous system. This requires special attention in term of public health recommendations.