{"paper_id":"aa4d3ae0-c2f5-42db-9905-022a5c791ad3","body_text":"Opinion\nVolume 12 Issue 1 - September 2018\nDOI: 10.19080/JGWH.2018.12.555829\nJ Gynecol Women’s Health\nCopyright © All rights are reserved by Jan Tesarik\nJ Gynecol Women’s Health 12(1): JGWH.MS.ID.555829 (2018) 001\nJournal of\nGynecology and Women’s Health\nISSN 2474-7602\nMelatonin: The First Noninvasive Causal Therapy  \nfor Both Endometriosis and Adenomyosis?\nJan Tesarik1* and Raquel Mendoza-Tesarik1,2\n1MARGen Clinic, Granada, Spain\n2University of Granada, Spain\nSubmission: September 17, 2018 ; Published: September 26, 2018\n*Corresponding author: Jan Tesarik, MARGen Clinic, University of Granada, Spain, Email: \nIntroduction\nIt was shown recently that melatonin inhibits 17 β-estradiol-\ninduced migration, invasion and epithelial-mesenchymal transition \nin normal and endometriotic human endometrial epithelial cells \n[1]. These data suggest that melatonin may become the first \nnoninvasive therapy which can be used to treat the very cause of \nendometriosis and not just to alleviate its symptoms. However, the \nbeneficial effect of melatonin, in addition to endometriosis, can \nbe expected exert similar effects in adenomyosis, another closely \nrelated pathology in which abnormally reactive endometrial \nepitelial cells are major players. In fact, the similarity of the \nrespective pathophysiological mechanisms of endometriosis and \nadenomyosis [2] suggests that melatonin may also be useful to \ntreat adenomyosis, another disease caused by aberrant behaviour \nof endometrial epithelial cells in response to 17β-estradiol. As for \nendometriosis, no noninvasive causal treatment for adenomyosis \nhas not been made available so far.\nBoth endometriosis and adenomyosis are characterized by \na profound alteration of cell signaling pathways, activated or \nsilenced by 17 β-estradiol, leading to epithelial-mesenchymal \ntransition (EMT) of the endometrial epithelial cells. As a result \nof these alterations, the endometrium-derived cells acquire the \nability to migrate to ectopic locations, to invade the adjacent tissues \nand to become resistent to apoptosis [3-4]. EMT is a physiological  \n \nprocess, involved in normal functioning of the female reproductive \norgans, but its dysregulation can lead to pathological conditions, \nsuch as endometriosis, adenomyosis, and carcinogenesis [5].\nThe findings by Qi et al. [1] show that melatonin counteracts \nthe estradiol-induced activation of the Notch pathway, which is \na key signaling pathway not only in EMT but also in the reverse \nprocess, referred to as mesenchymal-epithelial transition (MET). \nThe latter is associated with a loss of cell migratory freedom, \nrestriction of invasiveness and cancer regression [6]. The finding \nthat, in addition to estradiol-induced EMT , melatonin abolishes \nEMT induced by transforming growth factor (TGF)- b1 [1] suggests \nthat melatonin may also be effective against cancer. Interestingly, \nmelatonin has recently been shown to suppress fibrotic responses \nof a human mucoepidermoid cell line to TGF-b1 [7], suggesting \nthat this drug may be involved in both EMT and MET regulations. \nThese properties make melatonin an interesting candidate for \nboth the prevention and treatment of endometriosis [1] and \nadenomyosis [8-10].\nConclusion\nthe study by Qi et al. [1] should encourage further In vitro  \nstudies evaluating the effects of melatonin on the EMT and MET \nprocesses in human cells obtained by biopsy of organs affected by \ndifferent invasive pathologies, including adenomyosis and cancer. \nAbstract\nRecently published data show that in vitro exposure of human normal and endometriotic endometrial epithelial cells to melatonin inhibits \n17-estradiol-induced cell signaling pathways leading to their epithelial-mesenchymal transition, suggesting that melatonin might be used \nas a causative treatment agent for endometriosis. However, the same aberrant response of endometrial epithelial cells to 17 -estradiol is \nintimately associated with the pathophysiology of adenomyosis, another challenging issue to both clinicians and researchers. The eventual In \nvitro effects of melatonin on epithelial-mesenchymal transition and the reverse process, mesenchymal-epithelial transition of adenomyotic \ncells obtained by biopsy, remain to be evaluated. Moreover, clinical research into the effects of melatonin in women suffering from endometriosis \nand adenomyosis, including dose-finding studies, should be encouraged.\nKeywords: Endometriosis; Adenomyosis; Melatonin; Epithelial-mesenchymal transition; Mesenchymal-epithelial transition; 17 -estradiol; \nMigration and invasion\nAbbreviations: EMT: Epithelial-Mesenchymal Transition; TGF: Transforming Growth Factor\n\n\nHow to cite this article:  Jan T, Raquel M-T. Melatonin: Melatonin: The First Noninvasive Causal Therapy for Both Endometriosis and Adenomyosis?.  J \nGynecol Women’s Health. 2018: 12(1): 555829. DOI: 10.19080/JGWH.2018.12.555829.002\nJournal of Gynecology and Women’s Health\nIndependently, the time appears ready for designing clinical dose-\nfinding studies on In vivo  effects of melatonin on endometriotic \nand adenomyotic cells from affected women.\nReferences\n1. Qi S, Yan L, Liu Z, Mu YI, Li M, et al. (2018) Melatonin inhibits \n17β-estradiol-induced migration, invasion and epitelial-mesenchymal \ntransition in normal and endometriotic endometrial epithelial cells. \nReprod Biol Endocrinol 16(1): 62.\n2. Leyendecker G, Wildt L, Mall G (2009) The pathophysiology of \nendometriosis and adenomyosis: tissue injury and repair. Arch Gynecol \nObstet 280(4): 529-538.\n3. Chen YJ, Li HY, Huang CH, Twu NF, Yen MS, et al. (2010) Oestrogen-\ninduced epithelial-mesenchymal transition of endometrial epithelial \ncells contributes to the development of adenomyosis. J Pathol 222(3): \n261-270.\n4. Benagiano G, Brosens I, Habiba M (2014) Structural and molecular \nfeatures of the endomyometrium in endometriosis and adenomyosis. \nHum Reprod Update 20(3): 386-402.\n5. Bilyk O, Coatham M, Jewer M, Postovit LM (2017) Epithelial-to-\nmesenchymal transition in the female reproductive tract: From normal \nfunctioning to disease pathology. Front Oncol 7:145.\n6. Nieto MA, Huang RY, Jackson RA, Thiery JP (2016) EMT: 2016. Cell \n166(1): 21-45.\n7. Shin NR, Park JW, Lee IC, Ko JW, Park SH, et al. (2017) Melatonin \nsuppresses fibrotic responses induced by cigarette smoke via \ndownregulation of TGF-β1 Oncotarget 8(56): 95692-95703.\n8. Zhou W, Peng Z, Zhang C, Liu S, Zhang Y, et al. (2018) ILK-induced \nepithelial-mesenchymal transition promotes the invasive phenotype in \nadenomyosis. Biochem Biophys Res Commun 497(4): 950-956.\n9. Viswanathan AN, Schernhammer ES (2009) Circulating melatonin \nand the risk of breast and endometrial cancer in women. Cancer Lett \n281(1): 1-7.\n10. Chuffa LGA, Reiter RJ, Lupi LA (2017) Melatonin as a promising agent to \ntreat ovarian cancer: molecular mechanisms. Carcinogenesis 38(10): \n945-952.\nYour next submission with Juniper Publishers    \n      will reach you the below assets\n• Quality Editorial service\n• Swift Peer Review\n• Reprints availability\n• E-prints Service\n• Manuscript Podcast for convenient understanding\n• Global attainment for your research\n• Manuscript accessibility in different formats \n         ( Pdf, E-pub, Full Text, Audio) \n• Unceasing customer service\n                   Track the below URL for one-step submission \n         https://juniperpublishers.com/online-submission.php\nThis work is licensed under Creative\nCommons Attribution 4.0 License\nDOI: 10.19080/JGWH.2018.12.555829","source_license":"CC0","license_restricted":false}