Epigenetic Landscapes of Endometriosis: From Pathogenesis to Precision Medicine

In: Acta Universitatis Lodziensis. Folia Biologica et Oecologica · 2024 · vol. 18 , pp. 91–109 · doi:10.18778/1730-2366.18.13 · W4402599691
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This review outlines how epigenetic alterations, including DNA methylation and non-coding RNA dysregulation, contribute to endometriosis pathogenesis and offers insights into potential diagnostic biomarkers and targeted therapies.

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This review discusses how epigenetic alterations contribute to endometriosis pathogenesis, emphasizing studies of endometrial cells and related molecular mechanisms using evidence from histone modifications, DNA methylation, and non-coding RNA dysregulation. It reports that epigenetic dysregulation disrupts cellular homeostasis and hormone responsiveness—particularly progesterone responsiveness—by altering chromatin structure and gene expression, with examples including roles for histone methylation/acetylation and regulators such as CFP1 in progesterone receptor signaling. The review also describes biomarker findings for specific miRNAs and lncRNAs and outlines research on siRNA-based approaches targeting key genes, while noting the need for future work to clarify the interplay among epigenetic regulators and disease pathways. This paper is centrally about endometriosis — it synthesizes evidence on epigenetic landscapes spanning pathogenesis, biomarkers, and potential precision-medicine targets in endometriosis.

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Abstract

Endometriosis, a challenging gynecological disorder characterized by the ectopic presence of endometrial-like tissue, presents significant diagnostic and therapeutic hurdles due to its complex etiology and diverse clinical manifestations. Recent advancements in understanding its pathogenesis have underscored the pivotal role of epigenetic alterations, offering new insights into disease mechanisms and therapeutic targets. Epigenetic changes in endometrial cells significantly contribute to endometriosis pathogenesis, disrupting normal physiology and hormone responsiveness, particularly to progesterone. Dysregulation of histone modifications, DNA methylation, and non-coding RNA expression disrupts cellular homeostasis and promotes disease progression. Histone modifications, notably methylation and acetylation, influence chromatin structure and gene expression, affecting progesterone responsiveness and disease progression. Epigenetic regulators such as Cfp1 modulate progesterone receptor expression and downstream signalling pathways, presenting potential therapeutic targets. Non-coding RNAs, including miRNAs and lncRNAs, exert regulatory effects on gene expression and are implicated in endometriosis pathogenesis. Dysregulated expression disrupts cellular homeostasis and promotes disease progression. Biomarker studies have identified specific miRNAs and lncRNAs associated with endometriosis, offering avenues for non-invasive diagnosis and targeted therapies. siRNA-based therapies targeting key genes involved in endometriosis pathogenesis show promise as novel treatment modalities. By modulating gene expression and cellular functions, siRNA-based therapies offer a targeted approach to mitigate pathological processes. In this review, we summarize recent findings in the molecular mechanisms and regulatory pathways of endometriosis, offering valuable insights into pathology and therapeutic interventions. Future research efforts aimed at elucidating the complex interplay between epigenetic regulators and disease pathways hold promise for innovative diagnostic tools and targeted therapies.
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Epigenetic Landscapes of Endometriosis: From Pathogenesis to Precision Medicine DOI: https://doi.org/10.18778/1730-2366.18.13Keywords: endometriosis, epigenetic, infertility, pathogenesis of endometriosisAbstract Endometriosis, a challenging gynecological disorder characterized by the ectopic presence of endometrial-like tissue, presents significant diagnostic and therapeutic hurdles due to its complex etiology and diverse clinical manifestations. Recent advancements in understanding its pathogenesis have underscored the pivotal role of epigenetic alterations, offering new insights into disease mechanisms and therapeutic targets. Epigenetic changes in endometrial cells significantly contribute to endometriosis pathogenesis, disrupting normal physiology and hormone responsiveness, particularly to progesterone. Dysregulation of histone modifications, DNA methylation, and non-coding RNA expression disrupts cellular homeostasis and promotes disease progression. Histone modifications, notably methylation and acetylation, influence chromatin structure and gene expression, affecting progesterone responsiveness and disease progression. Epigenetic regulators such as Cfp1 modulate progesterone receptor expression and downstream signalling pathways, presenting potential therapeutic targets. Non-coding RNAs, including miRNAs and lncRNAs, exert regulatory effects on gene expression and are implicated in endometriosis pathogenesis. Dysregulated expression disrupts cellular homeostasis and promotes disease progression. Biomarker studies have identified specific miRNAs and lncRNAs associated with endometriosis, offering avenues for non-invasive diagnosis and targeted therapies. siRNA-based therapies targeting key genes involved in endometriosis pathogenesis show promise as novel treatment modalities. By modulating gene expression and cellular functions, siRNA-based therapies offer a targeted approach to mitigate pathological processes. In this review, we summarize recent findings in the molecular mechanisms and regulatory pathways of endometriosis, offering valuable insights into pathology and therapeutic interventions. Future research efforts aimed at elucidating the complex interplay between epigenetic regulators and disease pathways hold promise for innovative diagnostic tools and targeted therapies. Downloads References Abbaszadeh, M., Karimi, M., Rajaei, S. 2023. The landscape of non-coding RNAs in the immunopathogenesis of Endometriosis. Frontiers in Immunology, 14, 1223828. DOI: https://doi.org/10.3389/fimmu.2023.1223828 Adamczyk, M., Wender-Ozegowska, E., Kedzia, M. 2022. Epigenetic Factors in Eutopic Endometrium in Women with Endometriosis and Infertility. International Journal of Molecular Sciences, 23(7), 3804. DOI: https://doi.org/10.3390/ijms23073804 Afshar, Y., Hastings, J., Roqueiro, D., Jeong, J.W., Giudice, L.C., Fazleabas, A.T. 2013. 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DOI: https://doi.org/10.1055/s-0036-1585408 Żeberkiewicz, M., Hyc, A., Iwan, A., Zwierzchowska, A., Ścieżyńska, A., Kalaszczyńska, I., Barcz, E., Malejczyk, J. 2022. Expression of Fucosyltransferase 4 (FUT4) mRNA Is Increased in Endometrium from Women with Endometriosis. Journal of Clinical Medicine, 11(19), 5606. DOI: https://doi.org/10.3390/jcm11195606 Downloads Published Issue Section License This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

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