Behavior, Neural Structure, and Metabolism in Adult Male Mice Exposed to Environmentally Relevant Doses of Di(2-ethylhexyl) Phthalate Alone or in a Phthalate Mixture

• DOI: 10.1289/ehp11514
• Publication Date: 2023-07-17T14:45:58Z
• Authors: Suzanne Ducroq; Eric Duplus; Lucille Penalva-M...; Francesca Trivelloni; Aurore L’honoré; Caroline Chabat-C...; Ivan Nemazanyy; Valérie Grange-Me...; Isabelle Petropoulos; Sakina Mhaouty-Kodja
• Keywords: Male; Mice, Inbred C57BL; Mice; Research; Diethylhexyl Phthalate; Tryptophan; Phthalic Acids; Animals; Female; Kynurenine

Background: We have previously shown that chronic exposure of adult male mice to low doses di(2-ethylhexyl) phthalate (DEHP) altered sexual behavior and induced down-regulation the androgen receptor (AR) in neural circuitry controlling this behavior. Objectives: The cellular mechanisms by DEHP alone or an environmental mixture were studied. Methods: Two-month-old C57BL/6J males exposed orally for 8 wk (0, 5, 50μg/kg/d) (50μg/kg/d) a mixture. Behavior, dendritic density per 50-μm length, pre-/postsynaptic markers, synapse ultrastructure, bioenergetic activity analyzed. Results: Mice either differed mating, emission ultrasonic vocalizations, ability attract receptive females urinary preference tests from control mice. Analyses medial preoptic area, key hypothalamic region involved behavior, showed lower spine protein levels glutamate receptors differences other postsynaptic components presynaptic markers between treated groups. Ultrastructural observation synapses electron microscopy comparable morphology Metabolic analyses highlighted metabolites compared These included tryptophan higher NAD+ levels, respectively, precursor end product kynurenine pathway metabolism. amounts xenobiotic aryl hydrocarbon receptor, one targets metabolic known negative regulator AR, area Discussion: Differences phthalates associated with structure metabolism, possibly role metabolism effects mediated these substances. https://doi.org/10.1289/EHP11514