Open AccessThe transgenerational inheritance of autism-like phenotypes in mice exposed to valproic acid during pregnancy
Author(s) -
Chang Soon Choi,
Edson Luck Gonzales,
Ki Chan Kim,
Sung Min Yang,
Ji Woon Kim,
Darine Froy N. Mabunga,
Jae Hoon Cheong,
SeolHeui Han,
Geon Ho Bahn,
Chan Young Shin
Publication year - 2016
Publication title -
scientific reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 213
ISSN - 2045-2322
DOI - 10.1038/srep36250
Subject(s) - epigenetics , offspring , valproic acid , transgenerational epigenetics , phenotype , autism , inheritance (genetic algorithm) , autism spectrum disorder , epilepsy , biology , neuroscience , genetics , pregnancy , psychology , developmental psychology , gene
Autism spectrum disorder (ASD) is a heterogeneously pervasive developmental disorder in which various genetic and environmental factors are believed to underlie its development. Recently, epigenetics has been suggested as a novel concept for ASD aetiology with a proposition that epigenetic marks can be transgenerationally inherited. Based on this assumption of epigenetics, we investigated the transgenerational inheritance of ASD-like behaviours and their related synaptic changes in the VPA animal model of ASD. The first generation (F1) VPA-exposed offspring exhibited autistic-like impaired sociability and increased marble burying. They also showed increased seizure susceptibility, hyperactivity and decreased anxiety. We mated the VPA-exposed F1 male offspring with naïve females to produce the second generation (F2), and then similarly mated the F2 to deliver the third generation (F3). Remarkably, the autism-like behavioural phenotypes found in F1 persisted to the F2 and F3. Additionally, the frontal cortices of F1 and F3 showed some imbalanced expressions of excitatory/inhibitory synaptic markers, suggesting a transgenerational epigenetic inheritance. These results open the idea that E/I imbalance and ASD-like behavioural changes induced by environmental insults in mice can be epigenetically transmitted, at least, to the third generation. This study could help explain the unprecedented increase in ASD prevalence.