Genome-wide DNA methylation profiling in ectopic and eutopic of endometrial tissues

Purpose Endometriosis is a gynecological disease that causes the uterine lining to appear in other organs outside the uterus. As DNA methylation has an important role in this disorder, its profiling can reveal new information to improve the diagnosis and treatment of endometriosis patients.

We conducted a genome-wide methylation profiling of ectopic and eutopic endometrial tissues from women with and without endometriosis using Infinium Human Methylation 450K BeadChip arrays. DNA methylation samples were collected from nine ectopic and nine eutopic endometrial tissues of endometriosis and six endometrial tissues of healthy controls.

Correlation heatmaps and the principal component analysis divided the samples into two clusters, one consisting of all ectopic samples and the other consisting of both eutopic and control samples unexpectedly without segregation between them. The assay identified a group of methylated genes that were overrepresented in biological processes, including abnormality in signaling, development, and adhesion of cells. Pathway analysis revealed disruption in HTLV infection pathways, PI3K-Akt, oxytocin, and relaxin signaling. Moreover, we found eutopic lesions are strongly associated with autoimmune disease.

Our results confirmed the role of DNA methylation alternations in endometriosis development and pathogenesis. Our finding suggests aberrant DNA methylation can activate several signaling pathways including PI3k-AKT signaling, relaxin, and oxytocin which are associated with the pathogenesis of endometriosis. Similar content being viewed by others

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Biochim Biophys Acta. 2002;1573(3):394–405. Acknowledgments The authors have great appreciations for the kind support of Professor Saadi Khochbin in the generation of the methylome data. We also thank the gynecologist Dr. Fariba Ramazanali for preparing samples. Funding This project was partially supported by the Royan Institute (Grant No. 96000045). Author information Authors and Affiliations Corresponding author Ethics declarations Conflict of interests The authors declare that they have no conflicts of interest in the research. Additional information Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Maryam Shahhoseini is a co-corresponding author. Rights and permissions About this article Cite this article Barjaste, N., Shahhoseini, M., Afsharian, P. et al. Genome-wide DNA methylation profiling in ectopic and eutopic of endometrial tissues. J Assist Reprod Genet 36, 1743–1752 (2019). https://doi.org/10.1007/s10815-019-01508-8 Received: Accepted: Published: Version of record: Issue date: DOI: https://doi.org/10.1007/s10815-019-01508-8