Browsing by Author "Rahmioglu, Nilufer"

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Challenges in endometriosis miRNA studies - From tissue heterogeneity to disease specific miRNAs.
(2017) Saare, Merli; Rekker, Kadri; Laisk-Podar, Triin; Rahmioglu, Nilufer; Zondervan, Krina; Salumets, Andres; Götte, Martin; Peters, Maire
In order to uncover miRNA changes in endometriosis pathogenesis, both endometriotic lesions and endometrial biopsies, as well as stromal and epithelial cells isolated from these tissues have been investigated and a large number of dysregulated miRNAs have been reported. However, the concordance between the result of different studies has remained small. One potential explanation for limited overlap between the proposed disease-related miRNAs could be the heterogeneity in tissue composition, as some studies have compared highly heterogeneous whole-lesion biopsies with endometrial tissue, some have compared the endometrium from patients and controls, and some have used pure cell fractions isolated from lesions and endometrium. This review focuses on the results of published miRNA studies in endometriosis to reveal the potential impact of tissue heterogeneity on the discovery of disease-specific miRNA alterations in endometriosis. Additionally, functional studies that explore the roles of endometriosis-involved miRNAs are discussed.
Large-scale meta-analysis highlights the hypothalamic–pituitary–gonadal axis in the genetic regulation of menstrual cycle length
(Human Molecular Genetics, 2018) Laisk, Triin; Kukuškina, Viktorija; Palmer, Duncan; Laber, Samantha; Chen, Chia-Yen; Ferreira, Teresa; Rahmioglu, Nilufer; Zondervan, Krina; Becker, Christian; Smoller, Jordan W; Lippincott, Margaret; Salumets, Andres; Granne, Ingrid; Seminara, Stephanie; Neale, Benjamin; Mägi, Reedik; Lindgren, Cecilia M
The normal menstrual cycle requires a delicate interplay between the hypothalamus, pituitary and ovary. Therefore, its length is an important indicator of female reproductive health. Menstrual cycle length has been shown to be partially controlled by genetic factors, especially in the follicle-stimulating hormone beta-subunit (FSHB) locus. A genome-wide association study meta-analysis of menstrual cycle length in 44 871 women of European ancestry confirmed the previously observed association with the FSHB locus and identified four additional novel signals in, or near, the GNRH1, PGR, NR5A2 and INS-IGF2 genes. These findings not only confirm the role of the hypothalamic–pituitary–gonadal axis in the genetic regulation of menstrual cycle length but also highlight potential novel local regulatory mechanisms, such as those mediated by IGF2.
The influence of menstrual cycle and endometriosis on endometrial methylome
(Clin Epigenetics, 2016-01) Saare, Merli; Modhukur, Vijayachitra; Suhorutshenko, Marina; Rajashekar, Balaji; Rekker, Kadri; Sõritsa, Deniss; Karro, Helle; Soplepmann, Pille; Sõritsa, Andrei; Lindgren, Cecilia M; Rahmioglu, Nilufer; Drong, Alexander; Becker, Christian M; Zondervan, Krina T; Salumets, Andres; Peters, Maire
BACKGROUND: Alterations in endometrial DNA methylation profile have been proposed as one potential mechanism initiating the development of endometriosis. However, the normal endometrial methylome is influenced by the cyclic hormonal changes, and the menstrual cycle phase-dependent epigenetic signature should be considered when studying endometrial disorders. So far, no studies have been performed to evaluate the menstrual cycle influences and endometriosis-specific endometrial methylation pattern at the same time. RESULTS: Infinium HumanMethylation 450K BeadChip arrays were used to explore DNA methylation profiles of endometrial tissues from various menstrual cycle phases from 31 patients with endometriosis and 24 healthy women. The DNA methylation profile of patients and controls was highly similar and only 28 differentially methylated regions (DMRs) between patients and controls were found. However, the overall magnitude of the methylation differences between patients and controls was rather small (Δβ ranging from -0.01 to -0.16 and from 0.01 to 0.08, respectively, for hypo- and hypermethylated CpGs). Unsupervised hierarchical clustering of the methylation data divided endometrial samples based on the menstrual cycle phase rather than diseased/non-diseased status. Further analysis revealed a number of menstrual cycle phase-specific epigenetic changes with largest changes occurring during the late-secretory and menstrual phases when substantial rearrangements of endometrial tissue take place. Comparison of cycle phase- and endometriosis-specific methylation profile changes revealed that 13 out of 28 endometriosis-specific DMRs were present in both datasets. CONCLUSIONS: The results of our study accentuate the importance of considering normal cyclic epigenetic changes in studies investigating endometrium-related disease-specific methylation patterns.