Autism spectrum disorder-like behavior induced in rat offspring by perinatal exposure to di-(2-ethylhexyl) phthalate

Abstract

Autism spectrum disorders (ASD), also known as childhood autism, is a common neurological developmental disorder. Although it is generally believed that genetic factors are a primary cause for ASD development, more and more studies show that an increasing number of ASD diagnoses are related to environmental exposure. Epidemiological studies indicated that perinatal exposure to endocrine disruptors might cause neurodevelopmental disorders in children. Di-(2-ethylhexyl) phthalate (DEHP) is widely used as a plasticizer in many products. To explore the neurodevelopmental effect induced by perinatal exposure to DEHP on rat offspring, and the potential mechanisms, female Wistar rats were exposed to 1, 10, and 100 mg/kg/day DEHP during pregnancy and lactation, while valproic acid (VPA) was used as a positive control. The behavior tests showed that rat pups exposed to VPA and 100 mg/kg/day DEHP were not good as those from the control group in both their socialability and social novelty. Expression of mTOR pathway-related components increased while the number of autophagosomes decreased in the brain tissue of the rat offspring exposed to 100 mg/kg/day DEHP. In addition, perinatal exposure to DEHP at all dosages decreased the level of autophagy proteins LC3II and Beclin1 in the brain tissue of rat pups. Our results indicated that perinatal DEHP exposure would induce ASD-like behavioral changes in rat offspring, which might be mediated by activation of the mTOR signaling pathway, and inhibition of autophagy in the brain.

Keywords: ASD-like behavior; Autophagy; DEHP; mTOR signaling pathway.