New Approach to the Investigation of DOHaD Using X-inactivation Gene Expression System

Abstract

X-chromosome inactivation (XCI) occurs during the gestation period to compensate for the dosage of X-linked genes in female mammals. Xist RNA is a long noncoding RNA with a global epigenetic function and is indispensable for XCI from the initiation to establishment and maintenance phases. The X chromosome contains over 1,000 genes that are essential for proper development, especially that of the brain, immune system, metabolism and reproductive functions. We found that exposure to bisphenol A or folate deficiency during the fetal period changes the expressions of Xist, Tsix (the antisense repressor of Xist), and many X chromosome linked genes widely in newborn mice. This finding suggests that this X-chromosome mediated effect is considered one of the mechanisms of various problems encountered in the fetal environment. The Developmental Origins of Health and Disease (DOHaD) hypothesis states that nutrition and other environmental stimuli during critical periods affect developmental pathways with epigenetics and induce metabolism and chronic disease susceptibility. The XCI process has some similarities to this hypothesis and it may become one of the approaches to reveal the DOHaD mechanisms.