Work

Altered proteome, astrocyte activation and reduced structural plasticity and progesterone sensitivity in the ventromedial hypothalamus were associated with disrupted sexual behavior in adult female mice exposed to environmentally relevant doses of phthalates

Year: 2026

Type: article

Abstract: We have previously shown that chronic exposure of adult female mice to environmentally relevant doses of di(2-ethylhexyl) phthalate (DEHP) alone or in a phthalate mixture reduced sexual behavior. The present study was conducted to determine the associated molecular and cellular modifications occurring in the ventromedial hypothalamus (VMH), the brain area controlling this behavior. Adult C57BL/6 J female mice were fed with chow diet containing the vehicle, DEHP alone at 5 (DEHP-5) or 50 µg/kg/d (DEHP-50), or DEHP-5 in a phthalate mixture. Proteomic analysis of the VMH identified 532 differentially expressed proteins between the vehicle and the two DEHP doses; differences were also seen between DEHP-5 and DEHP-50. Gene ontology enrichment analysis identified biological processes related to several cellular functions including metabolism, immune response, glutamatergic neurotransmission and gene transcription related to sex steroids. Immunohistochemical analyses indicated astrocyte activation along with elevated immunoreactivity of pro-inflammatory inducible nitric oxide synthase, and reduced laminin-immunoreactivity in the VMH of females exposed to DEHP alone or in a phthalate mixture. The number and phenotype of microglia were not affected. Additional analyses showed reduced dendritic spine density and expression levels of postsynaptic markers, as well as down-regulation of the progesterone receptor and up-regulation of aryl hydrocarbon receptor in the VMH. These data strongly suggest that exposure to environmentally relevant doses of DEHP alone or in a phthalate mixture impaired the proteome of the VMH, leading to cellular alterations including reduced sensitivity to progesterone, diminished structural neuroplasticity and increased neuroinflammation, all possibly underlying impaired behavioral processing in female mice.

Source: Journal of Hazardous Materials

DOI: 10.1016/j.jhazmat.2026.142582

Authors: Nolwenn Adam, Manon Letard, Valérie Grange-Messent, Elodie Desroziers, Sakina Mhaouty-Kodja

Institutions: Centre National de la Recherche Scientifique, Inserm, Sorbonne Université, Institut de Biologie Paris-Seine, Développement Adaptation et Vieillissement

Language: English

Topic: Effects and risks of endocrine disrupting chemicals

Subfield: Health, Toxicology and Mutagenesis

Field: Environmental Science

Domain: Physical Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $4,340