Maternal Factors that Induce Epigenetic Changes Contribute to Neurological Disorders in Offspring

Abstract

It is well established that the regulation of epigenetic factors, including chromatic reorganization, histone modifications, DNA methylation, and miRNA regulation, is critical for the normal development and functioning of the human brain. There are a number of maternal factors influencing epigenetic pathways such as lifestyle, including diet, alcohol consumption, and smoking, as well as age and infections (viral or bacterial). Genetic and metabolic alterations such as obesity, gestational diabetes mellitus (GDM), and thyroidism alter epigenetic mechanisms, thereby contributing to neurodevelopmental disorders (NDs) such as embryonic neural tube defects (NTDs), autism, Down's syndrome, Rett syndrome, and later onset of neuropsychological deficits. This review comprehensively describes the recent findings in the epigenetic landscape contributing to altered molecular profiles resulting in NDs. Furthermore, we will discuss potential avenues for future research to identify diagnostic markers and therapeutic epi-drugs to reverse these abnormalities in the brain as epigenetic marks are plastic and reversible in nature.

Keywords: attention-deficit hyperactivity disorder (ADHD); epigenetics; fetal development; lifestyle; maternal factors; neurodevelopmental disorders.

Figure 1

Smoking in mothers alters neurodevelopmental processes in the fetus. Maternal smoking alters the DNA methylation of genes involved in placental and fetal development, leading to neurodevelopmental disorders in the offspring.

Figure 2

Epigenetic targets of alcohol exposure in the fetus. Gestational alcohol exposure induces histone modification, alteration in DNA methylation pattern and miRNA targets, and expression of genes associated with fetal developmental process, leading to neurodevelopmental disorders.

Figure 3

Effect of maternal dietary deficiency on fetal development. The absence of essential dietary supplements in maternal diet during gestation leads to a disruption in metabolic pathways and several epigenetic alterations in the fetus, triggering abnormal uterine development and neurodevelopmental disorders.

Figure 4

Effect of maternal metabolic conditions on fetal development. Metabolic conditions at gestation such as GDM, obesity, and hypothyroidism induce epigenetic alterations in the fetus, leading to a series of metabolic and immunogenic changes triggering neuroanatomical and neuropsychological deficits in the developing brain.

Figure 5

Maternal factor-induced epigenetic etiology for neurodevelopmental disorders. Several lifestyle-related metabolic factors and infection at gestation play a critical role in the epigenetic modification and in turn the altered expression of many genes associated with abnormal fetal development. This may lead to a series of neurodevelopmental disorders in the offspring.