ArrayExpress Uploader0mousewild typecontrolwild typecontrolwild typecontrolwild typeprenatal stresswild typeprenatal stresswild typeprenatal stress5HTT +/-control5HTT +/-control5HTT +/-control5HTT +/-prenatal stress5HTT +/-prenatal stress5HTT +/-prenatal stress6302arrayexpress_sid6prenatal stress response, genetic modification Background: Prenatal stress (PS) exposure has been shown to increase the risk for...E-GEOD-26025/profile/8773/arrayexpressuploader212cytokinegenomehippocampusserotoninDec.12, 2014Falsesex-specific-effects-of-prenatal-stress-in-5-htt-dE-GEOD-26025_A-AFFY-45Sex-specific effects of prenatal stress in 5-Htt deficient mice: towards molecular mechanisms of gene x environment interactionsNov.11, 2014prenatal stress response, genetic modification Background: Prenatal stress (PS) exposure has been shown to increase the risk for emotional disorders in later life. Furthermore, the serotonin transporter (5-HTT) genotype is suggested to exert a modulating effect on the association between early life stress and the risk for depression. In the present study, we use a 5-HTT x PS paradigm to investigate whether the effects of PS are dependent upon the 5-HTT genotype. Methods: The effects of PS on cognition, anxiety- and depression-related behaviour were examined using a maternal restraint stress paradigm of PS in C57BL6 wild-type (WT) and heterozygous (+/-) 5-HTT knockout mice. Additionally, in the female offspring, a genome-wide hippocampal gene expression screening was performed. Results: 5-HTT +/- offspring showed enhanced memory performance and signs of reduced anxiety as compared to WT offspring. Conversely, exposure of 5-HTT +/- mice to PS was associated with altered stress-responsivity and increased depressive-like behaviour, particularly in female offspring. Further, 5-HTT genotype, PS and their interaction differentially affected the expression of numerous genes and related pathways within the female hippocampus. Specifically, MAPK and neurotrophin signalling were regulated by both the 5-HTT +/- genotype and PS exposure, whereas cytokine and Wnt signalling were affected in a 5-HTT genotype x PS manner, indicating a gene x environment interaction at the molecular level. Conclusions: The long-term behavioural effects of PS in C57BL6 mice are partly dependent on the 5-HTT genotype. Further, hippocampal gene expression profiles suggest that distinct molecular mechanisms mediate the behavioural effects of the 5-HTT genotype, PS exposure, and their interaction. total samples analysed are 12http://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-26025http://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-26025/samples/