Gene expression changes in mouse fetal fibroblasts after chronic exposure to simulated space conditions

Space conditions including microgravity and cosmic radiation are difficult to simulate on Earth. However, ground-based models exist to simulate space flight conditions including irradiation (IR) facilities and µg simulating devices such as the Random Positioning Machine (RPM). In this study, a space simulating experimental model was used to monitor gene expression changes in primary skin fibroblasts obtained from mouse fetus. Cells were continuously exposed (65h) to a low dose (55mSv) IR mixture of neutrons and γ-rays and/or simulated microgravity (RPM), after which whole genome microarrays were performed. Two different analytical methods to detect changes in gene expression were used in parallel in this study including 'single gene analysis' and 'Gene Set Enrichment Analysis'. Our results show that simulated microgravity affected fetal murine fibroblasts by inducing oxidative stress responsive genes and decreasing the expression of genes involved in cytoskeleton remodeling. Similarly, chronic exposure to low dose IR caused a down-regulation of genes involved in cytoskeleton pathways, but also in genes involved in cell cycle regulation and DNA damage response. Many of the genes or gene sets that were altered in the individual treatments were not significantly changed in the combined treatment, indicating no synergistic effect between RPM and IR.