Alteration of the Early Development Environment by Maternal Diet and the Occurrence of Autistic-like Phenotypes in Rat Offspring.

Kinga Gawlińska,Małgorzata Jarmuż-Szymczak,Ewelina Kowal-Wiśniewska,Dawid Gawliński,Małgorzata Filip

doi:10.3390/ijms22189662

Abstract

Epidemiological and preclinical studies suggest that maternal obesity increases the risk of autism spectrum disorder (ASD) in offspring. Here, we assessed the effects of exposure to modified maternal diets limited to pregnancy and lactation on brain development and behavior in rat offspring of both sexes. Among the studied diets, a maternal high-fat diet (HFD) disturbed the expression of ASD-related genes (Cacna1d, Nlgn3, and Shank1) and proteins (SHANK1 and TAOK2) in the prefrontal cortex of male offspring during adolescence. In addition, a maternal high-fat diet induced epigenetic changes by increasing cortical global DNA methylation and the expression of miR-423 and miR-494. As well as the molecular changes, behavioral studies have shown male-specific disturbances in social interaction and an increase in repetitive behavior during adolescence. Most of the observed changes disappeared in adulthood. In conclusion, we demonstrated the contribution of a maternal HFD to the predisposition to an ASD-like phenotype in male adolescent offspring, while a protective effect occurred in females.

Highlights

The importance of nutrition to neonatal health during fetal development is highlighted by decades of studies with the Developmental Origins of Health and Disease (DOHaD)theory, which proposes that adverse in-utero conditions can influence developmental pathways in early life that result in long-term changes to offspring health and disease susceptibility [1,2]
In adolescent male offspring (PND 28), maternal high-fat diet (HFD) significantly increased the expression of the Cacna1d (p < 0.05), Nlgn3 (p < 0.05), and Shank1 (p < 0.05) genes, and a similar trend was observed for Taok2 (p = 0.07); maternal HCD elevated En2 expression (p < 0.05) compared to the standard diet (SD) group (Figure 1B)
To support that the development of autism spectrum disorder (ASD) is caused by a complex interaction between genetic and environmental factors, mainly related to epigenetic mechanisms [20], and because the pathogenesis of ASD is thought to mainly lie in the periods of the three trimesters of pregnancy and the initial postpartum period [21,22], we investigated the effect of exposure to modified maternal diets (HFD, HCD, and MD) limited to pregnancy and lactation on the susceptibility to ASD symptoms in male and female rat offspring

Summary

Introduction

The importance of nutrition to neonatal health during fetal development is highlighted by decades of studies with the Developmental Origins of Health and Disease (DOHaD)theory, which proposes that adverse in-utero conditions can influence developmental pathways in early life that result in long-term changes to offspring health and disease susceptibility [1,2]. The importance of nutrition to neonatal health during fetal development is highlighted by decades of studies with the Developmental Origins of Health and Disease (DOHaD). Despite the key role of maternal nutrition in the development and function of the offspring brain [3,4], a limited number of studies leave many interesting questions unanswered. It has been shown that maternal obesity and exposure to a high-fat diet (HFD) during early development are associated with an increased risk of developing serious mental health and behavioral disorders, including anxiety, depression, attention deficit hyperactivity disorder (ADHD), and schizophrenia, in offspring [5]. The search for the pathogenic mechanisms and risk factors for this complex disease, as well as understanding the sex differences that lead to a significantly more frequent diagnosis of ASD in boys, is very important

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