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Abstract
BackgroundHuman embryonic stem cells (hESCs) potentially offer new routes to study, on the basis of the Developmental Origins of Health and Disease (DOHaD) concept, how the maternal environment during pregnancy influences the offspring’s health and can predispose to chronic disease in later life. Reactive oxygen species (ROS), antioxidant defences and cellular redox status play a key function in gene expression regulation and are involved in diabetes and metabolic syndromes as in ageing.MethodsWe have, therefore, designed an in vitro cell model of oxidative stress by exposing hESCs to hydrogen peroxide (H2O2) during 72 h, in order to resemble the period of preimplantation embryonic development.ResultsWe have analysed the global gene expression profiles of hESCs (HUES3) exposed to non-cytotoxic H2O2 concentrations, using Illumina microarray HT-12 v4, and we found the differential expression of 569 upregulated and 485 downregulated genes. The most affected gene ontology categories were those related with RNA processing and splicing, oxidation reduction and sterol metabolic processes. We compared our findings with a published RNA-seq profiling dataset of human embryos developed in vitro, thereupon exposed to oxidative stress, and we observed that one of the common downregulated genes between this publication and our data, NEDD1, is involved in centrosome structure and function.ConclusionsTherefore, we assessed the presence of supernumerary centrosomes and showed that the percentage of cells with more than two centrosomes increased acutely with H2O2 treatment in hESCs (HUES3 and 7) and in a control somatic cell line (Hs27), inducing a premature entry into senescence.
Highlights
Human embryonic stem cells potentially offer new routes to study, on the basis of the Developmental Origins of Health and Disease (DOHaD) concept, how the maternal environment during pregnancy influences the offspring’s health and can predispose to chronic disease in later life
Transcriptome analysis In a preliminary study we developed [19] a novel in vitro model to analyse the effects of oxidative stress and the antioxidant response against reactive oxygen species (ROS) in embryonic stem cells compared with somatic cells
No global differences were observed in the transcriptome profile between samples of different H2O2 conditions (Additional file 3: Figure S2), suggesting that the global gene expression of human ES cells is stable upon hydrogen peroxide treatment
Summary
Human embryonic stem cells (hESCs) potentially offer new routes to study, on the basis of the Developmental Origins of Health and Disease (DOHaD) concept, how the maternal environment during pregnancy influences the offspring’s health and can predispose to chronic disease in later life. When ROS production exceeds cellular defences, these unstable compounds can damage proteins, nucleic acids and lipids [1]. This situation is known as oxidative stress, and it has been related to the ageing process and to. Cell culture has been used for many decades to decode the mechanisms involved in oxidative stress and to analyse the protective effect of antioxidants, providing a vast amount of information. HESCs provide the in vitro model to study how early human embryonic cells react to an adverse environment during the critical preimplantation window when environmental alterations like oxidative stress can lead to future disorders, according to the Developmental Origins of Health and Disease theory (DOHaD) [10]
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