Metabolic Dysfunction As a Legacy of Paternal Preconception Ethanol Abuse
Abstract
It is now well-accepted that parental history and exposures encountered prior to conception exert a significant impact on offspring health through epigenetic means, and in some cases, have the potential to induce the development of disease later in life. Preliminary studies in our lab have identified prenatal / postnatal growth restriction and altered epigenetic programming in a mouse model of chronic, preconception male alcohol exposure. These studies challenge the current maternal-centric exposure paradigm and implicate paternal exposure history as an additional mediator of alcohol-induced defects. In clinical studies, fetal growth restriction is associated with the early onset of multiple adult diseases including type II diabetes, non-alcoholic fatty liver disease and a collection of pathologies commonly referred to as metabolic syndrome. How prenatal growth restriction is able to induce this sequela is poorly understood. Recently, disruptions in complex networks of genes regulated through genomic imprinting have emerged as major regulators of metabolism. In this study, we assayed the expression of genes participating in these imprinted regulatory networks within the placenta and fetal liver. Using real-time qPCR, we measured the expression of transcripts encoding the imprinted genes Cdkn1c, Dcn, Dlk1, Gatm, Gnas, Gh2, Grb10, H19, Igf2, Igf2r, Mest, Ndn, Sgce, Meg3, Peg3,Zac1 and Slc38a4. From these assays, we observed altered expression of select imprinted genes, including Grb10 (males) and Sgce (females) in the placenta, as well as Cdkn1c (males) and GH2 (females) in the fetal liver. However, all of these candidate genes exhibited decreased expression with no evidence of inappropriate contributions from the normally silent paternal allele. Thus, there is likely another transcriptional mechanism at the root of this growth phenotype.
Citation
Sutton, Gabrielle Isabella (2018). Metabolic Dysfunction As a Legacy of Paternal Preconception Ethanol Abuse. Undergraduate Research Scholars Program. Available electronically from https : / /hdl .handle .net /1969 .1 /177579.