Hypertrophic Gene Expression in An In Vitro Patho-logical Model of XX and XY Human Embryonic Stem Cells (hESCs)-Derived Cardiomyocytes

Gender-specific phenotypes of the cardiovascular system have been reported with respect to both physiology and pathology. While most of these sex-related differences have been associated with the sex hormones, molecular biology stud-ies have assigned roles to the differential expression of genes from which many are located on X-Y chromosomes. Therefore, in the present study, we sought to investigate the expression of the cardiac-specific genes in samples provided by cardiogenic differentiation of XX and XY human embryonic stem cells (hESCs) during different stages of differentiation in hormone-free setups.Materials and Methods: We sought to investigate the expres-sion of hypertrophic genes in XX and XY hESC-derived car-diomyocytes subjected to in vitro hypetrophy induction. Quan-titative Real-Time PCR was used for gene expression analysis. Results: The sex-related RPS۴X gene showed down-regulation in males at days ۶ and ۱۲ of cardiac differentiation. The results of in vitro hypertrophy induction indicated that female cardio-myocytes were less sensitive to pathological stimulation be-cause hypertrophy induction was achieved with higher doses of hypertrophy stimulant; isoproterenol. The ratio of NPPB/NPPA gene expression was significantly higher in hypertrophied male cardiomyocytes indicating a more relevant response. Interest-ingly, the expression of KDM۵C of X chromosome was up-regulated in hypertrophied male cardiomyocytes.Conclusion: In summary, our results may provide evidences on the direct contribution of differential gene expression on sexual dimorphism observed in physiological and pathological charac-teristics of cardiomyocytes.