Environmental Influences on Genomic Imprinting

Abstract

Genomic imprinting refers to the epigenetic mechanism that results in the mono-allelic expression of a subset of genes in a parent-of-origin manner. These haploid genes are highly active in the placenta and are functionally implicated in the appropriate development of the fetus. Furthermore, the epigenetic marks regulating imprinted expression patterns are established early in development. These characteristics make genomic imprinting a potentially useful biomarker for environmental insults, especially during the in utero or early development stages, and for health outcomes later in life. Herein, we critically review the current literature regarding environmental influences on imprinted genes and summarize findings that suggest that imprinted loci are sensitive to known teratogenic agents, such as alcohol and tobacco, as well as less established factors with the potential to manipulate the in utero environment, including assisted reproductive technology. Finally, we discuss the potential of genomic imprinting to serve as an environmental sensor during early development.

Neurodevelopmental consequences in offspring of mothers with preeclampsia during pregnancy: underlying biological mechanism via imprinting genes

“…In two small pilot studies on 50 placenta samples from the Stress in Pregnancy (SIP) Study, we found both an alteration of the methylation profile of the ICR that regulates the parent-of-origin-specific expression of two key imprinted genes, IGF2 and H19 (imprinted in the opposite direction), in correlation with maternal stress in pregnancy and an alteration of the global DNA methylation in correlation with preeclampsia [72]. We also found that imprinted gene expression in the placenta correlates with fetal growth and development, as measured by head circumference and birth weight [87, 108]. Furthermore, the imprinting status of each imprinted locus, as defined by the ICR methylation status, has been shown to exert different effects on the reactivation of the silent allele of imprinted genes at that specific locus [91, 108].…”

Effects of Prenatal Exposure to Endocrine Disruptors and Toxic Metals on The Fetal Epigenome

“…Interestingly, it has been shown that methylation at imprinted loci are stable across a wide range of human tissues in infants, suggesting that the observed changes in imprinted genes may be representative of changes occurring throughout the fetus [141]. The ability for such exposures to alter genomic imprinting is concerning given the tight regulation of imprinting during development and the impact that the expression of imprinted genes has on health throughout the lifespan [142]. Thus, the relationships between heavy metals, endocrine disruptors and methylation of imprinted genes should be further examined.…”

Maternal residential air pollution and placental imprinted gene expression

“…Environmental exposures have been associated with numerous types of epigenetic changes, including imprinted gene regulation (Kappil et al 2015b; Marsit 2015). Genomic imprinting arises early in fetal development and it has been suggested that these epigenetic patterns may function as a biosensor for the impact of in utero environmental exposures (Hoyo et al 2009; Jirtle and Skinner 2007).…”

“…For example, loss of genomic imprinting (LOI) early in development can lead to placental and fetal growth restriction (Lambertini et al 2012a), and recent studies have shown that even relatively modest differences in imprinted gene expression are associated with fetal growth/birth weight (Kappil et al 2015a; Lambertini et al 2012b). Moreover, in both human and animal studies imprinted gene expression has been associated with exposure to a number of environmental exposures, including, maternal nutrition, alcohol use, tobacco use, and BPA exposure, and imprinted gene expression has been highlighted as a potentially useful environmental sensor (Kappil et al 2015b). …”