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Browsing by Author "Rämö, Karita"

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  • Rämö, Karita (2022)
    Every year in the western world 3–5% of newborns suffer permanent damages due to prenatal alcohol exposure. Alcohol causes the symptoms of Fetal Alcohol Spectrum Disorders (FASD), which consist of various structural, cognitive, and behavioral neurological defects and distinctive craniofacial features, although in many cases the condition is undiagnosed. The frequency, amount, and timing of alcohol consumption during pregnancy critically influence the symptoms and their severity. Despite the serious consequences and frequent incidence, there is still no clear information on the etiology of FASD symptoms or the timing specific effects of alcohol. However, it has been hypothesized that the early pregnancy is especially susceptible to environmental exposures, such as alcohol, because there is rapid cell proliferation, cell differentiation, and epigenetic reprogramming taking place in the embryo. Gastrulation is a crucial developmental stage in early embryonic development where the three germ layers, endoderm, mesoderm, and ectoderm form and create a foundation for all further development. The aims of this thesis are to study how alcohol affects the gene expression in undifferentiated human embryonic stem cells (hESCs) compared to cells differentiating into the germ layers, and how the gene expression in each of the germ layers is affected. To study the differentiation in gastrulation, hESCs were differentiated in vitro under alcohol exposure to endoderm, mesoderm, and ectoderm with STEMdiff™ Trilineage Differentiation Kit. Gene expression in differentiated germ layers and undifferentiated hESCs was analyzed with 3’mRNA sequencing. The results show that the number of genes with alcohol-induced differential expression is considerably higher in hESCs than in the germ layers indicating that undifferentiated hESCs are more susceptible to alcohol than differentiating cells, which is in agreement with findings from previous studies. In the germ layers, alcohol affected the expression of many genes involved in developmentally important signaling pathways such as FGF, Wnt, and TGF-β. Each of the germ layers have different gene expression profiles and accordingly, they exhibit a unique response to alcohol. Furthermore, the differentially expressed genes reveal intriguing connections to the FASD phenotype, notably, in ectodermal cells alcohol caused differential expression in many genes related to neurodevelopment.