Maternal Exposure to Di-(2-ethylhexyl) Phthalate Impairs Hippocampal Synaptic Plasticity in Male Offspring: Involvement of Damage to Dendritic Spine Development.

Abstract

Exposure to di-(2-ethylhexyl) phthalate (DEHP), a widely used kind of plasticizer, can result in neurodevelopment impairments and learning and memory disorders. We studied the effects and possible mechanisms of maternal DEHP treatment on hippocampal synaptic plasticity in offspring. Pregnant Wistar rats were randomly divided into four groups and received 0, 30, 300, 750 (mg/kg)/d DEHP by gavage from gestational day (GD) 0 to postnatal day (PN) 21. Our data showed that DEHP exposure impaired hippocampal synaptic plasticity, damaged synaptic ultrastructure, and decreased synaptic protein levels in male pups. Furthermore, DEHP decreased the density of dendritic spines, affected F-actin polymerization, and downregulated the Rac1/PAK/LIMK1/cofilin signaling pathway in male offspring. However, the alterations in the hippocampi of female offspring were not observed. These results illustrate that maternal DEHP exposure could impair hippocampal synaptic plasticity by affecting synaptic structure and dendritic spine development in male offspring, which may be attributed to altered cytoskeleton construction induced by downregulation of the Rac1/PAK/LIMK1/cofilin signaling pathway.