Prenatal and postnatal exposure to butylparaben induces neurodevelopmental disorders in mice offspring

Butylparaben (BP) is a chemical commonly used as a preservative, but it is an endocrine-disrupting chemical (EDC) with estrogenic activity in humans when exposed through various routes. Although the adverse effects of BP have been confirmed, the neurodevelopmental toxicity of BP is still unclear. The neurotoxic effects of BP were confirmed in vitro, leading to an investigation of its impact on the neurodevelopment of mouse offspring in this study. BP caused a reduction in cell viability (IC₅₀=3.56x10^-4 M) and neural differentiation (ID₅₀=6.14x10^-4 M) in a developmental neurotoxicity test using 46C mouse neural progenitor cells, confirming its neurotoxic potential. A behavioral evaluation was carried out on the offspring mice. The pups were exposed to BP from early pregnancy (embryo day 10.5) until the weaning day (postnatal day 20), as their mothers were orally administered BP at doses of 50 or 100 mg/kg/day. The effects of BP on the offspring's behavior were studied. Male offspring exposed to BP showed impaired memory (novel object recognition and Morris water maze tests; p<0.05 or lower), and suggested social deficits (three-chamber test). Female offspring demonstrated increased compulsive behavior (marble burying test; p<0.05), impaired memory (Morris water maze; p<0.001) and reduced spontaneous locomotion (open field test; p<0.05). Gene expression analysis revealed elevated levels of AChE and NMDAr mRNA in a sex-dependent manner (p<0.05 or lower). These findings support that BP induces neurodevelopmental toxicity via cholinergic and glutamatergic disruption, suggesting its potential risk even at sub-toxic doses.