Browsing by Author "Zondervan, K."

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    DNA methylation alterations—potential cause of endometriosis pathogenesis or a reflection of tissue heterogeneity?
    (2018) Salumets, A.; Kaplinski, L.; Saare, M.; Krigul, KL.; Laisk-Podar, T.; Ponandai-Srinivasan, S.; Rahmioglu, N.; Lalit Kumar, PG.; Zondervan, K.; Peters, M.
    Alterations in the DNA methylation pattern of endometriotic lesions and endometrium of endometriosis patients have been proposed as one potential factor accompanying the endometriosis development. Although many differentially methylated genes have been associated with the pathogenesis of this disease, the overlap between the results of different studies has remained small. Among other potential confounders, the impact of tissue heterogeneity on the outcome of DNA methylation studies should be considered, as tissues are mixtures of different cell types with their own specific DNA methylation signatures. This review focuses on the results of DNA methylation studies in endometriosis from the cellular heterogeneity perspective. We consider both the studies using highly heterogeneous whole-lesion biopsies and endometrial tissue, as well as pure cell fractions isolated from lesions and endometrium to understand the potential impact of the cellular composition to the results of endometriosis DNA methylation studies. Also, future perspectives on how to diminish the impact of tissue heterogeneity in similar studies are provided.
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    DNA methylation changes in endometrium and correlation with gene expression during the transition from pre-receptive to receptive phase
    (2017) Kukushkina, V.; Modhukur, V.; Suhorutšenko, M.; Peters, M.; Mägi, R.; Rahmioglu, N.; Velthut-Meikas, A.; Altmäe, S.; Esteban, FJ.; Vilo, J.; Zondervan, K.; Salumets, A.; Laisk-Podar, T.
    The inner uterine lining (endometrium) is a unique tissue going through remarkable changes each menstrual cycle. Endometrium has its characteristic DNA methylation profile, although not much is known about the endometrial methylome changes throughout the menstrual cycle. The impact of methylome changes on gene expression and thereby on the function of the tissue, including establishing receptivity to implanting embryo, is also unclear. Therefore, this study used genome-wide technologies to characterize the methylome and the correlation between DNA methylation and gene expression in endometrial biopsies collected from 17 healthy fertile-aged women from pre-receptive and receptive phase within one menstrual cycle. Our study showed that the overall methylome remains relatively stable during this stage of the menstrual cycle, with small-scale changes affecting 5% of the studied CpG sites (22,272 out of studied 437,022 CpGs, FDR < 0.05). Of differentially methylated CpG sites with the largest absolute changes in methylation level, approximately 30% correlated with gene expression measured by RNA sequencing, with negative correlations being more common in 5′ UTR and positive correlations in the gene ‘Body’ region. According to our results, extracellular matrix organization and immune response are the pathways most affected by methylation changes during the transition from pre-receptive to receptive phase.