{"paper_id":"ca413aae-5bd7-4d28-b3ac-e86580b53c64","body_text":"Mini Review\nVolume 4 Issue 3 - May 2017\nDOI: 10.19080/JGWH.2017.04.555637\nJ Gynecol Women’s Health\nCopyright © All rights are reserved by Guoyun Wang\nA possible Molecular Mechanism of Adenomyosis\nGuoyun Wang*\nDepartment of Obstetrics and Gynecology, Qilu Hospital of Shandong University, China\nSubmission: April 09, 2017 ; Published: May 02, 2017\n*Corresponding author: Guoyun Wang, Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan 250012, China,  \nTel: ; Email: \nJ Gynecol Women’s Health 4(3): JGWH.MS.ID.555637 (2017)\nMini Review\nAdenomyosis, an estrogen-dependent inflammatory disease, \nis defined as the presence of endometrial glands and stroma \ndeep within the myometrium [1]. The main clinical features \nof adenomyosis are dysmenorrhea and menorrhagia, which \nare significantly associated with peritoneal endometriosis \nin infertile patients at reproductive age [2,3]. The only \ndifference between adenomyosis and endometriosis is the \nsite of endometriotic tissues, that is, inside or outside the \nuterus [4]. Thus, knowledge on the endometriotic cell origin is \nindispensable for the development of preventive and targeted \ntreatment strategies for adenomyosis. The most widely accepted \ntheory on the pathogenesis of adenomyosis is the down growth \nand invagination of the endometrium into the myometrium [5]. \nHowever, the possible mechanism of gland invagination from the \nendometrium deep into the underlying myometrium is unknown.\nEpithelial mesenchymal transition (EMT) and its converse, \nmesenchymal epithelial transition (MET), are concepts defined \ndecades ago [6]. Once epithelial cells become competent to \nrespond to EMT-inducing signals, these signals can promote the \ndisruption of the intercellular adhesion complexes and the loss \nof the apicobasal polarity of the epithelial cells, a prime feature \ncrucial for cells to leave the epithelium and achieve migration \npotentiality [7]. Many studies indicated that EMT is a crucial \nprocess in adenomyosis and endometriosis lesions [8,9], and \nthe endometrium and inner myometrium are closely apposed \nwithout any intervening basement membrane; thus, EMT events \nmight occur here.\nMacrophages have been known to play important roles in \nthe adenomyosis process [4]. One study reported an increased \nstromal macrophage population in the functional layer of \nthe endometrium in patients experiencing diffuse and focal \nadenomyosis [10]. Another study indicated that, after treating \nadenomyosis patients with the gonadotrophin releasing \nhormone (GnRH) agonist, the infiltration of CD68-positive \nmacrophages is significantly decreased in the endometrium of \nadenomyotic women [11]. \nAbnormal levels of macrophages, which are important \ncomponents of immune cells, have been largely reported in \nadenomyosis [12]. Increased knowledge on the immune aspects \nof the pathogenesis of adenomyosis is needed for this debilitating \ncondition. To our knowledge, macrophages, which play important \nroles in innate and acquired immunity, together with natural \nkiller cells and cytotoxic T-lymphocytes in healthy women, can \ndestroy misplaced endometrial cells [13]. The EMT process \ninduced by macrophages has been investigated systematically in \ntissue repair, remodeling, fibrosis [14], and tumor progression \n[15]. Alternatively activated (M2) macrophages are the major \ntype associated with the tumor EMT process. Similar to tumor \nprogression, adenomyosis also exhibits the EMT process.\nGiven that macrophages and EMT are all involved in the \nadenomyosis process, and the definite mechanism by which \nmacrophages promote the development of adenomyosis is \nvague, we presumed that macrophages may induce endometrial \nepithelial cells to undergo EMT , because macrophages can \ninduce EMT in many other diseases. Thus, EMT induced by \nmacrophages might be an effective molecular mechanism to \npromote adenomyosis.\nAdenomyosis, an estrogen-dependent inflammatory disease, \nis defined as the presence of endometrial glands and stroma \ndeep within the myometrium [1]. The main clinical features \nof adenomyosis are dysmenorrhea and menorrhagia, which \nare significantly associated with peritoneal endometriosis \nin infertile patients at reproductive age [2,3]. The only \ndifference between adenomyosis and endometriosis is the \nsite of endometriotic tissues, that is, inside or outside the \nuterus [4]. Thus, knowledge on the endometriotic cell origin is \nindispensable for the development of preventive and targeted \ntreatment strategies for adenomyosis. The most widely accepted \ntheory on the pathogenesis of adenomyosis is the down growth \nand invagination of the endometrium into the myometrium [5]. \nHowever, the possible mechanism of gland invagination from the \nendometrium deep into the underlying myometrium is unknown.\n001\nJournal of\nGynecology and Women’s Health\nISSN 2474-7602\n\n\nHow to cite this article: Guoyun Wang. A possible Molecular Mechanism of Adenomyosis. J Gynecol Women’s Health 2017; 4(3): 555637. DOI: 10.19080/\nJGWH.2017.04.555637002\nJournal of Gynecology and Women’s Health\nEpithelial mesenchymal transition (EMT) and its converse, \nmesenchymal epithelial transition (MET), are concepts defined \ndecades ago [6]. Once epithelial cells become competent to \nrespond to EMT-inducing signals, these signals can promote the \ndisruption of the intercellular adhesion complexes and the loss \nof the apicobasal polarity of the epithelial cells, a prime feature \ncrucial for cells to leave the epithelium and achieve migration \npotentiality [7]. Many studies indicated that EMT is a crucial \nprocess in adenomyosis and endometriosis lesions [8,9], and \nthe endometrium and inner myometrium are closely apposed \nwithout any intervening basement membrane; thus, EMT events \nmight occur here.\nMacrophages have been known to play important roles in \nthe adenomyosis process [4]. One study reported an increased \nstromal macrophage population in the functional layer of \nthe endometrium in patients experiencing diffuse and focal \nadenomyosis [10]. Another study indicated that, after treating \nadenomyosis patients with the gonadotrophin releasing \nhormone (GnRH) agonist, the infiltration of CD68-positive \nmacrophages is significantly decreased in the endometrium of \nadenomyotic women [11]. \nAbnormal levels of macrophages, which are important \ncomponents of immune cells, have been largely reported in \nadenomyosis [12]. Increased knowledge on the immune aspects \nof the pathogenesis of adenomyosis is needed for this debilitating \ncondition. To our knowledge, macrophages, which play important \nroles in innate and acquired immunity, together with natural \nkiller cells and cytotoxic T-lymphocytes in healthy women, can \ndestroy misplaced endometrial cells [13]. The EMT process \ninduced by macrophages has been investigated systematically in \ntissue repair, remodeling, fibrosis [14], and tumor progression \n[15]. Alternatively activated (M2) macrophages are the major \ntype associated with the tumor EMT process. Similar to tumor \nprogression, adenomyosis also exhibits the EMT process.\nGiven that macrophages and EMT are all involved in the \nadenomyosis process, and the definite mechanism by which \nmacrophages promote the development of adenomyosis is \nvague, we presumed that macrophages may induce endometrial \nepithelial cells to undergo EMT , because macrophages can \ninduce EMT in many other diseases. Thus, EMT induced by \nmacrophages might be an effective molecular mechanism to \npromote adenomyosis.\nReferences\n1. Ferenczy A (1998) Pathophysiology of adenomyosis. Human \nReproduction Update 4(4): 312-322.\n2. Khan KN, Kitajima M, Hiraki K, Fujishita A, Sekine I, et al. (2010) \nChanges in tissue inflammation, angiogenesis and apoptosis in \nendometriosis, adenomyosis and uterine myoma after GnRH agonist \ntherapy. Hum Reprod 25(3): 642-653.\n3. Kunz G, Beil D, Huppert P , Leyendecker G (2000) Structural \nabnormalities of the uterine wall in women with endometriosis and \ninfertility visualized by vaginal sonography and magnetic resonance \nimaging. Hum Reprod 15(1): 76-82.\n4. Ota H, Igarashi S, Hatazawa J, Tanaka T (1998) Is adenomyosis an \nimmune disease? Human Reproduction Update 4(4): 360-367.\n5. Bergeron C, Amant F, Ferenczy A (2006) Pathology and physiopathology \nof adenomyosis. Best Pract Res Clin Obstet Gynaecol 20(4): 511-521.\n6. Alcorn D, Maric C, McCausland J (1999) Development of the renal \ninterstitium. Pediatr Nephrol 13(4): 347-354.\n7. Khan KN, Kitajima M, Hiraki K, Fujishita A, Nakashima M, Masuzaki \nH (2015) Involvement of Hepatocyte Growth Factor-Induced \nEpithelial-Mesenchymal Transition in Human Adenomyosis. Biology of \nReproduction 92(2): 35.\n8. Kunz G, Beil D, Huppert P , Noe M, Kissler S, et al. (2005) Adenomyosis \nin endometriosis--prevalence and impact on fertility. Evidence from \nmagnetic resonance imaging. Hum Reprod 20(8): 2309-2316.\n9. 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.\n10. Matsuzaki S, Darcha C (2012) Epithelial to mesenchymal transition-\nlike and mesenchymal to epithelial transition-like processes might \nbe involved in the pathogenesis of pelvic endometriosis. Human \nReproduction 27(3): 712-721.\n11. Tremellen KP , Russell P (2012) The distribution of immune cells \nand macrophages in the endometrium of women with recurrent \nreproductive failure. II: adenomyosis and macrophages. Journal of \nReproductive Immunology 93(1): 58-63.\n12. Khan KN, Kitajima M, Hiraki K, Fujishita A, Sekine I, et al. (2010) \nChanges in tissue inflammation, angiogenesis and apoptosis in \nendometriosis, adenomyosis and uterine myoma after GnRH agonist \ntherapy. Hum Reprod 25(3): 642-653.\n13. Dmowski WP , Gebel H, Braun DP (1998) Decreased apoptosis and \nsensitivity to macrophage mediated cytolysis of endometrial cells in \nendometriosis. Hum Reprod Update 4(5): 696-701.\n14. Scotton CJ, Chambers RC (2007) Molecular targets in pulmonary \nfibrosis: the myofibroblast in focus. Chest 132(4): 1311-1321.\n15. Galdiero MR, Garlanda C, Jaillon S, Marone G, Mantovani A (2013) \nTumor associated macrophages and neutrophils in tumor progression. \nJournal of Cellular Physiology 228(7): 1404-1412.\n\nHow to cite this article: Guoyun Wang. A possible Molecular Mechanism of Adenomyosis. J Gynecol Women’s Health 2017; 4(3): 555637. DOI: 10.19080/\nJGWH.2017.04.555637003\nJournal of Gynecology and Women’s Health\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 Licens\nDOI: 10.19080/JGWH.2017.04.555637","source_license":"CC0","license_restricted":false}