A maternal high-fat diet during early development provokes molecular changes related to autism spectrum disorder in the rat offspring brain

Abstract

Autism spectrum disorder (ASD) is a disruptive neurodevelopmental disorder manifested by abnormal social interactions, communication, emotional circuits, and repetitive behaviors and is more often diagnosed in boys than in girls. It is postulated that ASD is caused by a complex interaction between genetic and environmental factors. Epigenetics provides a mechanistic link between exposure to an unbalanced maternal diet and persistent modifications in gene expression levels that can lead to phenotype changes in the offspring. To better understand the impact of the early development environment on the risk of ASD in offspring, we assessed the effect of maternal high-fat (HFD), high-carbohydrate, and mixed diets on molecular changes in adolescent and young adult offspring frontal cortex and hippocampus. Our results showed that maternal HFD significantly altered the expression of 48 ASD-related genes in the frontal cortex of male offspring. Moreover, exposure to maternal HFD led to sex-and age-dependent changes in the protein levels of ANKRD11, EIF4E, NF1, SETD1B, SHANK1 and TAOK2, as well as differences in DNA methylation levels in the frontal cortex and hippocampus of the offspring. Taken together, it was concluded that a maternal HFD during pregnancy and lactation periods can lead to abnormal brain development within the transcription and translation of ASD-related genes mainly in male offspring.