{"paper_id":"8f76cfa3-3862-4831-b7d7-4404df0da80a","body_text":"Abstract\nPurpose\nAdenomyosis is a benign uterine disease resulting from the myometrial invasion of the endometrial gland and stroma. In the current study, angiogenesis, apoptosis and energy metabolism were investigated in adenomyosis.\nMethods\nA retrospective study was performed using paraffin archival tissues. Three groups were included in the study: Group I and Group II; ectopic and eutopic endometrial tissues of patients with adenomyosis, respectively, and Control Group; endometrial tissue of individuals without adenomyosis. Vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), intercellular adhesion molecule 1 (ICAM-1) and hypoxia-inducible factor 1 alpha (HIF-1A) levels were evaluated as angiogenic markers. Bcl-2, caspase-9 and caspase-3 levels were investigated as apoptotic indicators, and isocitrate dehydrogenase 1 (IDH1), succinate dehydrogenase complex subunit C (SDHC) and fumarate hydratase (FH) levels were also examined as energy metabolism markers. Gene expression levels of all parameters were determined by RT-PCR.\nResult\nVEGF expression levels were found to be increased in Group I according to the control group and Group II. Bcl-2 expression levels were found to be increased in the Group I compared to the Group II. It was determined that expression levels of IDH1 were decreased in the Group I and Group II compared to the Control Group. There was no significant difference in the other examined parameters. Although we did not find a significant difference in HIF-1A levels between the groups, we found a positive correlation between VEGF and HIF-1A in the Group I.\nConclusion\nThese results point out that VEGF, HIF-1A, Bcl-2 and IDH1 may be associated with the etiology of adenomyosis.\nSimilar content being viewed by others\nReferences\nAbbott JA (2017) Adenomyosis and abnormal uterine bleeding (AUB-A)-pathogenesis, diagnosis, and management. Best Pract Res Clin Obstet Gynaecol 40:68–81\nStruble J, Reid S, Bedaiwy MA (2016) Adenomyosis: a clinical review of a challenging gynecologic condition. J Minim Invasive Gynecol 23(2):164–185\nVannuccini S, Tosti C, Carmona F et al (2017) Pathogenesis of adenomyosis: an update on molecular mechanisms. Reprod Biomed Online 35(5):592–601\nKoike N, Tsunemi T, Uekuri C et al (2013) Pathogenesis and malignant transformation of adenomyosis. Oncol Rep 29(3):861–867\nGaravaglia E, Audrey S, Annalisa I et al (2015) Adenomyosis and its impact on women fertility. Iran J Reprod Med 13(6):327–336\nFerenczy A (1998) Pathophysiology of adenomyosis. Hum Reprod Update 4:312–322\nTaran FA, Stewart EA, Brucker S (2013) Adenomyosis: epidemiology, risk factors, clinical phenotype and surgical and interventional alternatives to hysterectomy. Geburtshilfe Frauenheilkd 73(9):924–931\nTakeda A, Sakai K, Mitsui T, Nakamura H (2007) Laparoscopic management of juvenile cystic adenomyoma of the uterus: report of two cases and review of the literature. J Minim Invasive Gynecol 14:370–374\nYuan H, Zhang S (2019) Malignant transformation of adenomyosis: literature review and meta-analysis. Arch Gynecol Obstet 299:47–53\nTempleman C, Marshall SF, Ursin G et al (2008) Adenomyosis and endometriosis in the California Teachers Study. Fertil Steril 90:415–424\nBergeron C, Amant F, Ferenczy A (2006) Pathology and physiopathology of adenomyosis. Best Pract Res Clin Obstet Gynaecol 20:511–521\nLeyendecker G, Wildt L, Mall G (2009) The pathophysiology of endometriosis and adenomyosis: tissue injury and repair. Arch Gynecol Obstet 280(4):529–538\nStreuli I, Dubuisson J, Santulli P et al (2014) An update on the pharmacological management of adenomyosis. Expert Opin Pharmacother 15:2347–2360\nBrosens I, Derwig I, Brosens J et al (2010) The enigmatic uterine junctional zone: the missing link between reproductive disorders and major obstetrical disorders? Hum Reprod 25:569–574\nGoteri G, Lucarini G, Montik N et al (2009) Expression of vascular endothelial growth factor (VEGF), hypoxia inducible factor-1alpha (HIF-1alpha), and microvessel density in endometrial tissue in women with adenomyosis. Int J Gynecol Pathol 28(2):157–163\nKang S, Zhao J, Liu Q et al (2009) Vascular endothelial growth factor gene polymorphisms are associated with the risk of developing adenomyosis. Environ Mol Mutagen 50(5):361–366\nJones RK, Searle RF, Bulmer JN (1998) Apoptosis and bcl-2 expression in normal human endometrium, endometriosis and adenomyosis. Hum Reprod 13(12):3496–3502\nGoumenou A, Panayiotides I, Matalliotakis I et al (2001) Bcl-2 and Bax expression in human endometriotic and adenomyotic tissues. Eur J Obstet Gynecol Reprod Biol 99(2):256–260\nKitawaki J (2006) Adenomyosis: the pathophysiology of an oestrogen-dependent disease. Best Pract Res Clin Obstet Gynaecol 20(4):493–502\nHever A, Roth RB, Hevezi PA et al (2006) Molecular characterization of human adenomyosis. Mol Hum Reprod 12(12):737–748\nHerndon CN, Aghajanova L, Balayan S et al (2016) Global transcriptome abnormalities of the eutopic endometrium from women with adenomyosis. Reprod Sci 23(10):1289–1303\nHan Y, Zhou Y, Zheng S (2002) Study on the expression of vascular endothelial growth factor in patients with adenomyosis of the uterus. Zhonghua Fu Chan Ke Za Zhi 37:539–541\nOrazov MR, Nosenko EN, Radzinsky VE et al (2016) Proangiogenic features in chronic pelvic pain caused by adenomyosis. Gynecol Endocrinol 32(sup2):7–10\nHanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144(5):646–674\nMorin A, Letouzé E, Gimenez-Roqueplo AP, Favier J (2014) Oncometabolites-driven tumorigenesis: from genetics to targeted therapy. Int J Cancer 135(10):2237–2248\nAtkins HM, Bharadwaj MS, O'Brien Cox A et al (2019) Endometrium and endometriosis tissue mitochondrial energy metabolism in a nonhuman primate model. Reprod Biol Endocrinol 17(1):70\nAcknowledgements\nThis study, which is the part of ‘‘Investigation of Angiogenesis, Apoptosis and Energy Metabolism in Adenomyosis’’ project, was funded by grants from Mersin University Research Foundation, Mersin, Turkey. (Grant no. 2017-2-TP3-2580)\nFunding\nThis study was supported by the Mersin University Research Foundation in Turkey with Project Number 2017-2-TP3-2580.\nAuthor information\nAuthors and Affiliations\nContributions\nCY: Project development, Data collection, Molecular analysis, Data analysis, Manuscript writing and editing. NC: Project advisor, Manuscript editing. İG: Data collection, Metodology. HA: Data collection, Clinic advisor. BT: Statistical analysis.\nCorresponding author\nEthics declarations\nConflict of interest\nNo authors have any financial/conflicting interests to disclose.\nEthical approval\nThis study, which is the part of ‘‘Investigation of Angiogenesis, Apoptosis and Energy Metabolism in Adenomyosis’’ project, was approved by the Ethics Committee of Mersin University (Mersin, Turkey) (13/04/2017, 93).\nAdditional information\nPublisher's Note\nSpringer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.\nRights and permissions\nAbout this article\nCite this article\nYalaza, C., Canacankatan, N., Gürses, İ. et al. Altered VEGF, Bcl-2 and IDH1 expression in patients with adenomyosis. Arch Gynecol Obstet 302, 1221–1227 (2020). https://doi.org/10.1007/s00404-020-05742-9\nReceived:\nAccepted:\nPublished:\nVersion of record:\nIssue date:\nDOI: https://doi.org/10.1007/s00404-020-05742-9","source_license":"CC0","license_restricted":false}