Placental DNA methylation profile as predicting marker for autism spectrum disorder (ASD)

Abstract

Autism spectrum disorder (ASD) is a neurodevelopmental disorder that impairs normal brain development and socio-cognitive abilities. The pathogenesis of this condition points out the involvement of genetic and environmental factors during in-utero life. Placenta, as an interface tissue between mother and fetus, provides developing fetus requirements and exposes it to maternal environment as well. Therefore, the alteration of DNA methylation as epigenetic consequence of gene-environmental interaction in the placenta could shed light on ASD pathogenesis. In this study, we reviewed the current findings on placental methylation status and its association with ASD. Differentially methylated regions (DMRs) in ASD-developing placenta were found to be mainly enriched in ASD gene loci affecting synaptogenesis, microtubule dynamics, neurogenesis and neuritogenesis. In addition, non-genic DMRs in ASD-placenta proposes an alternative contributing mechanism for ASD development. Our study highlights the importance of placental DNA methylation signature as a biomarker for ASD prediction.

Keywords: Autism; Brain; DNA methylation; Epigenetic; Placenta.

Fig. 1

Placenta-brain axis. By affecting the in utero environment, maternal exposures could influence placental methylation and in turn alter gene expression, resulting in brain development impairments, possibly contributing to the ASD development. (The figure was designed using Vecteezy images; www.vecteezy.com)

Fig. 2

Chromosomal locations of most important differentially methylated genes in ASD-Placenta. The colors in the ideograms show: black and grey: Giemsa positive, red: centromere, light blue: variable region, and dark blue: stalk