Prenatal epigenetic factors are predisposing for neurodevelopmental disorders-Considering placenta as a model

The heterogeneous characteristics of neurodevelopmental disorders (NDDs) have resulted in varied perspectives on their causation. The biology behind the phenotypic heterogeneity in NDDs is not yet well-defined, but a strong genetic basis has become well accepted as causal for NDDs. Alongside this, there is growing focus on epigenetic mechanisms. The evidence mounting for in-utero origins of NDDs has promoted research focused on epigenetic mechanisms that impact genes that program early brain development. Considering that placenta is a vital organ, this review emphasizes the prenatal factors and their effects on epigenetic changes influencing the normal functioning of the placenta, and factors mediating pathology in the developing fetus. Overall, it is an attempt to bring focus on the hypothesis that "Prenatal epigenetic factors in the placenta could be predisposing to NDDs (with special interest on autism spectrum disorders)." This review finds growing evidence for epigenetic modifications in the placenta that affect glucocorticoid, nutrient, and immune signaling pathways, eventually impacting fetal brain development. This evidence largely comes from animal models. Given the multicellular nature of placenta, we conclude that, there is a need for placental research focused on employing single-cell approaches and genome-wide methylation profiles to bring insights into specific molecular pathways in the placenta that regulate early brain development.