Effects of oxidative stress on human embryonic stem cells; global gene expression, advanced glycation end products and NEDD1 levels

Abstract

A number of unfavorable conditions can affect the development of the early embryo inducing oxidative stress both in vivo, for instance in gestational diabetes, and in vitro, when embryos are derived from Assisted Reproductive Technologies (ART). Human Embryonic Stem Cells (hESCs) potentially offer a unique in vitro model to study how an adverse environment during the early developmental stages post-fertilization can affect the physiology of the undifferentiated embryonic stem cells existing in the early embryo and predispose to long term effects on the offspring, according to the Developmental Origins of Health and Disease (DOHaD) concept. Therefore, the aim of this thesis was the development of a novel in vitro model to analyze the effects of oxidative stress and the antioxidant response against Reactive Oxygen Species (ROS) in hESC. This study demonstrates that, although non-cytotoxic hydrogen peroxide (H2O2) treatment have no effect on cellular viability or proliferation, the induced oxidative stress causes a significant increase in intracellular ROS and results in lipid peroxidation and advanced glycation end products accumulation. This is associated with a differential modulation between hES and somatic cells of gene expression, affecting gene ontology categories mainly related with RNA processing and splicing, oxidation-reduction and sterol metabolic processes.