Molecular Mechanisms of Premature Hippocampal and Hypothalamic Senescence Induced by Maternal Exposure to DBP in Male Offspring Mice

Dibutyl phthalate (DBP), a common plastic additive, is employed extensively to enhance the flexibility of various polymeric materials despite its known toxicity to multiple organ systems. Our previous study found that maternal DBP exposure caused early puberty in male offspring, but the effect on male brain aging was unclear. In this study, pregnant mice were orally administered corn oil (control) or varying doses of DBP via gavage from gestational day 12. The results demonstrated that prenatal DBP exposure induced premature aging in the hippocampus and hypothalamus of male offspring during adolescence and led to a cognitive decline in adulthood. In vitro analyses further showed that monobutyl phthalate (MBP), the principal DBP metabolite, promotes senescence in both HT22 hippocampal and GT1-7 GnRH neuronal cells by activating NF-κB signaling. Notably, the pharmacological inhibition of NF-κB using BAY 11-7082 significantly mitigated this senescence. This study provides the first evidence linking maternal DBP exposure to accelerated brain aging and precocious puberty in offspring, establishing a foundation for investigating DBP's role in aging-related toxicity.