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 20th century in Western countries could be linked to changes in diets and exposure to molecules from industry, such as endocrine disruptors and, among them, phthalates. The combined effects of a high fat/high fructose diet (HFHF) and exposure to an environmental mixture of phthalates (mix) were evaluated on male murine sexual behavior. Four groups of adult male C57Bl/6J mice were exposed 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 diets induced metabolic alterations but only the HFHFmix diet altered the efficiency of sexual behavior, with a dramatic decrease in the number of animals reaching ejaculation and a subsequent increase in mating latency. This was associated with a decrease in testicular, seminal glands and Tyson glands weights and a loss in discrimination toward female counterparts in an olfactory preference test. No effects were recorded on locomotion activity. In the HFHFmix group, the protein amounts of synaptophysin, dopamine transporter (DAT), and glutamate receptor AMPA GluR1, known as modulatory pathways of sexual behavior, were modified in the hypothalamic medial preoptic area, the main integrating center in the control of this behavior. The additional effect of an HFHF diet and phthalates, at doses relevant for human exposure, on male sexual behavior, could be thus explained by an alteration in this neural network, revealing a specific vulnerability that requires special attention in term of public health recommendations.