The Pathogenesis of Endometriosis: Are Endometrial Stem/Progenitor Cells Involved?

Meuleman C, Vandenabeele B, Fieuws S, Spiessens C, Timmerman D, D’Hooghe T (2009) High prevalence of endometriosis in infertile women with normal ovulation and normospermic partners. Fertil Steril 92:68–74. https://doi.org/10.1016/j.fertnstert.2008.04.056 Shafrir AL, Farland LV, Shah DK, Harris HR, Kvaskoff M, Zondervan K et al (2018) Risk for and consequences of endometriosis: a critical epidemiologic review. Best Pract Res Clin Obst Gynaecol 51:1–15. https://doi.org/10.1016/j.bpobgyn.2018.06.001 Hill CJ, Fakhreldin M, Maclean A, Dobson L, Nancarrow L, Bradfield A et al (2020) Endometriosis and the fallopian tubes: theories of origin and clinical implications. J Clin Med 9:1905. https://doi.org/10.3390/jcm9061905 Haas D, Chvatal R, Reichert B, Renner S, Shebl O, Binder H et al (2012) Endometriosis: a premenopausal disease? Age pattern in 42,079 patients with endometriosis. Arch Gynecol Obstet 286:667–760. https://doi.org/10.1007/s00404-012-2361-z Naem A, Shamandi A, Al-Shiekh A, Alsaid B (2020) Free large sized intra-abdominal endometrioma in a postmenopausal woman: a case report. BMC Womens Health 20:190. https://doi.org/10.1186/s12905-020-01054-x Koninckx PR, Ussia A, Adamyan L, Wattiez A, Gomel V, Martin DC (2019) Pathogenesis of endometriosis: the genetic/epigenetic theory. Fertil Steril 111:327–340. https://doi.org/10.1016/j.fertnstert.2018.10.013 Simpson JL, Elias S, Malinak LR, Buttram VC Jr (1980) Heritable aspects of endometriosis. I. Genetic studies. Am J Obstet Gynecol 137:327–331. https://doi.org/10.1016/0002-9378(80)90917-5 Coxhead D, Thomas EJ (1993) Familial inheritance of endometriosis in a British population. A case control study. J Obstet Gynaecol 13:42–44 Kennedy S (1998) The genetics of endometriosis. J Reprod Med 43(3 Suppl):263–268 Kennedy S, Hadfield R, Westbrook C, Weeks DE, Barlow D, Golding S (1998) Magnetic resonance imaging to assess familial risk in relatives of women with endometriosis. Lancet (London, England) 352:1440–1441. https://doi.org/10.1016/s0140-6736(05)61262-7 Carter JE (1994) Combined hysteroscopic and laparoscopic findings in patients with chronic pelvic pain. J Am Assoc Gynecol Laparosc 2:43–47. https://doi.org/10.1016/s1074-3804(05)80830-8 Sourial S, Tempest N, Hapangama DK (2014) Theories on the pathogenesis of endometriosis. Int J Reprod Med 2014:179515. https://doi.org/10.1155/2014/179515 Koninckx PR, Zupi E, Martin DC (2018) Endometriosis and pregnancy outcome. Fertil Steril 110:406–407. https://doi.org/10.1016/j.fertnstert.2018.06.029 Lee HJ, Park YM, Jee BC, Kim YB, Suh CS (2015) Various anatomic locations of surgically proven endometriosis: a single-center experience. Obstet Gynecol Sci 58:53–58. https://doi.org/10.5468/ogs.2015.58.1.53 Nisolle M, Donnez J (2019) Reprint of: peritoneal endometriosis, ovarian endometriosis, and adenomyotic nodules of the rectovaginal septum are three different entities. Fertil Steril 112(4 Suppl1):e125–e36. https://doi.org/10.1016/j.fertnstert.2019.08.081 Victory R, Diamond MP, Johns DA (2007) Villar’s nodule: a case report and systematic literature review of endometriosis externa of the umbilicus. J Min Invas Gynecol 14:23–32. https://doi.org/10.1016/j.jmig.2006.07.014 Gates J, Sharma A, Kumar A (2018) Rare case of thoracic endometriosis presenting with lung nodules and pneumothorax. BMJ Case Rep. https://doi.org/10.1136/bcr-2018-224181 Maniglio P, Ricciardi E, Meli F, Tomao F, Peiretti M, Caserta D (2018) Complete remission of cerebral endometriosis with dienogest: a case report. Gynecol Endocrinol 34:837–839. https://doi.org/10.1080/09513590.2018.1463362 Wang Y, Nicholes K, Shih IM (2020) The origin and pathogenesis of endometriosis. Annu Rev Pathol 15:71–95. https://doi.org/10.1146/annurev-pathmechdis-012419-032654 Liu Y, Zhang Z, Yang F, Wang H, Liang S, Wang H et al (2020) The role of endometrial stem cells in the pathogenesis of endometriosis and their application to its early diagnosis†. Biol Reprod 102:1153–1159. https://doi.org/10.1093/biolre/ioaa011 Sampson JA (1927) Peritoneal endometriosis due to the menstrual dissemination of endometrial tissue into the peritoneal cavity. Am J Obstet Gynecol 14:422–469 D’Hooghe TM, Debrock S (2003) Evidence that endometriosis results from the dislocation of basal endometrium? Hum Reprod (Oxford, England) 18:1130; author reply-1. https://doi.org/10.1093/humrep/deg182 Klemmt PAB, Starzinski-Powitz A (2018) Molecular and cellular pathogenesis of endometriosis. Curr Womens Health Rev 14:106–116. https://doi.org/10.2174/1573404813666170306163448 Brosens I, Benagiano G (2013) Is neonatal uterine bleeding involved in the pathogenesis of endometriosis as a source of stem cells? Fertil Steril 100:622–623. https://doi.org/10.1016/j.fertnstert.2013.04.046 Giannarini G, Scott CA, Moro U, Grossetti B, Pomara G, Selli C (2006) Cystic endometriosis of the epididymis. Urology 68:203.e1–3. https://doi.org/10.1016/j.urology.2006.01.017 Zanatta A, Rocha AM, Carvalho FM, Pereira RM, Taylor HS, Motta EL et al (2010) The role of the Hoxa10/HOXA10 gene in the etiology of endometriosis and its related infertility: a review. J Assist Reprod Genet 27:701–710. https://doi.org/10.1007/s10815-010-9471-y Laganà AS, Vitale SG, Salmeri FM, Triolo O, Ban Frangež H, Vrtačnik-Bokal E et al (2017) Unus pro omnibus, omnes pro uno: a novel, evidence-based, unifying theory for the pathogenesis of endometriosis. Med Hypotheses 103:10–20. https://doi.org/10.1016/j.mehy.2017.03.032 Makiyan Z (2017) Endometriosis origin from primordial germ cells. Organogenesis 13:95–102. https://doi.org/10.1080/15476278.2017.1323162 Taylor HS (2004) Endometrial cells derived from donor stem cells in bone marrow transplant recipients. JAMA 292:81–85. https://doi.org/10.1001/jama.292.1.81 Mints M, Jansson M, Sadeghi B, Westgren M, Uzunel M, Hassan M et al (2008) Endometrial endothelial cells are derived from donor stem cells in a bone marrow transplant recipient. Hum Reprod (Oxford, England) 23:139–143. https://doi.org/10.1093/humrep/dem342 Ikoma T, Kyo S, Maida Y, Ozaki S, Takakura M, Nakao S et al (2009) Bone marrow-derived cells from male donors can compose endometrial glands in female transplant recipients. Am J Obstet Gynecol 201:608.e1–8. https://doi.org/10.1016/j.ajog.2009.07.026 Ponandai-Srinivasan S, Andersson KL, Nister M, Saare M, Hassan HA, Varghese SJ et al (2018) Aberrant expression of genes associated with stemness and cancer in endometria and endometrioma in a subset of women with endometriosis. Hum Reprod (Oxford, England) 33:1924–1938. https://doi.org/10.1093/humrep/dey241 Song Y, Xiao L, Fu J, Huang W, Wang Q, Zhang X et al (2014) Increased expression of the pluripotency markers sex-determining region Y-box 2 and Nanog homeobox in ovarian endometriosis. Reprod Biol Endocrinol 12:42. https://doi.org/10.1186/1477-7827-12-42 Shariati F, Favaedi R, Ramazanali F, Ghoraeian P, Afsharian P, Aflatoonian B et al (2018) Increased expression of stemness genes REX-1, OCT-4, NANOG, and SOX-2 in women with ovarian endometriosis versus normal endometrium: a case-control study. Int J Reprod Biomed 2016. https://doi.org/10.18502/ijrm.v16i12.3684 Silveira CG, Abrão MS, Dias JA Jr, Coudry RA, Soares FA, Drigo SA et al (2012) Common chromosomal imbalances and stemness-related protein expression markers in endometriotic lesions from different anatomical sites: the potential role of stem cells. Hum Reprod (Oxford, England) 27:3187–3197. https://doi.org/10.1093/humrep/des282 Kyo S, Sato S, Nakayama K (2020) Cancer-associated mutations in normal human endometrium: surprise or expected? Cancer Sci 111:3458–3467. https://doi.org/10.1111/cas.14571 Mashayekhi P, Noruzinia M, Zeinali S, Khodaverdi S (2019) Endometriotic mesenchymal stem cells epigenetic pathogenesis: deregulation of miR-200b, miR-145, and let7b in A functional imbalanced epigenetic disease. Cell J 21:179–185. https://doi.org/10.22074/cellj.2019.5903 Liu XJ, Bai XG, Teng YL, Song L, Lu N, Yang RQ (2016) miRNA-15a-5p regulates VEGFA in endometrial mesenchymal stem cells and contributes to the pathogenesis of endometriosis. Eur Rev Medical Pharmacol Sci 20:3319–3326 Sadler TW, Langman’s medical embryology. Lippincott Williams & Wilkins Philadelphia LaRonde-LeBlanc NA, Wolberger C, Structure of HoxA9 and Pbx1 bound to DNA: hox hexapeptide and DNA recognition anterior to posterior. Genes Dev 17:2060–2072. https://doi.org/10.1101/gad.1103303 McGinnis W, Krumlauf R (1992) Homeobox genes and axial patterning. Cell 68:283–302. https://doi.org/10.1016/0092-8674(92)90471-n Capellini TD, Zewdu R, Di Giacomo G, Asciutti S, Kugler JE, Di Gregorio A et al (2008) Pbx1/Pbx2 govern axial skeletal development by controlling Polycomb and Hox in mesoderm and Pax1/Pax9 in sclerotome. Dev Biol 321:500–514. https://doi.org/10.1016/j.ydbio.2008.04.005 Schnabel CA, Godin RE, Cleary ML (2003) Pbx1 regulates nephrogenesis and ureteric branching in the developing kidney. Dev Biol 254:262–276. https://doi.org/10.1016/s0012-1606(02)00038-6 Schnabel CA, Selleri L, Jacobs Y, Warnke R, Cleary ML (2001) Expression of Pbx1b during mammalian organogenesis. Mech Dev 100:131–135. https://doi.org/10.1016/s0925-4773(00)00516-5 Schnabel CA, Selleri L, Cleary ML (2003) Pbx1 is essential for adrenal development and urogenital differentiation. Genesis (New York, NY: 2000) 37:123–130. https://doi.org/10.1002/gene.10235 Taylor HS, Vanden Heuvel GB, Igarashi P (1997) A conserved Hox axis in the mouse and human female reproductive system: late establishment and persistent adult expression of the Hoxa cluster genes. Biol Reprod 57:1338–1345. https://doi.org/10.1095/biolreprod57.6.1338 Cunha GR (1976) Stromal induction and specification of morphogenesis and cytodifferentiation of the epithelia of the Mullerian ducts and urogenital sinus during development of the uterus and vagina in mice. J Exp Zool 196:361–370. https://doi.org/10.1002/jez.1401960310 Branford WW, Benson GV, Ma L, Maas RL, Potter SS (2000) Characterization of Hoxa-10/Hoxa-11 transheterozygotes reveals functional redundancy and regulatory interactions. Dev Biol 224:373–387. https://doi.org/10.1006/dbio.2000.9809 Warot X, Fromental-Ramain C, Fraulob V, Chambon P, Dollé P (1997) Gene dosage-dependent effects of the Hoxa-13 and Hoxd-13 mutations on morphogenesis of the terminal parts of the digestive and urogenital tracts. Development (Cambridge, England) 124:4781–4791 Vainio S, Heikkilä M, Kispert A, Chin N, McMahon AP (1999) Female development in mammals is regulated by Wnt-4 signalling. Nature 397:405–409. https://doi.org/10.1038/17068 Miller C, Sassoon DA (1998) Wnt-7a maintains appropriate uterine patterning during the development of the mouse female reproductive tract. Development (Cambridge, England) 125:3201–3211 Mericskay M, Kitajewski J, Sassoon D (2004) Wnt5a is required for proper epithelial-mesenchymal interactions in the uterus. Development (Cambridge, England) 131:2061–2072. https://doi.org/10.1242/dev.01090 Selleri L, Depew MJ, Jacobs Y, Chanda SK, Tsang KY, Cheah KS et al (2001) Requirement for Pbx1 in skeletal patterning and programming chondrocyte proliferation and differentiation. Development (Cambridge, England) 128:3543–3557 Hayashi K, Yoshioka S, Reardon SN, Rucker EB 3rd, Spencer TE, DeMayo FJ et al (2011) WNTs in the neonatal mouse uterus: potential regulation of endometrial gland development. Bio Reprod 84:308–319. https://doi.org/10.1095/biolreprod.110.088161 Serrano-Gomez SJ, Maziveyi M, Alahari SK (2016) Regulation of epithelial-mesenchymal transition through epigenetic and post-translational modifications. Mol Cancer 15:18. https://doi.org/10.1186/s12943-016-0502-x Gargett CE (2007) Uterine stem cells: what is the evidence? Hum Reprod Update 13:87–101. https://doi.org/10.1093/humupd/dml045 Makiyan Z (2016) New theory of uterovaginal embryogenesis. Organogenesis 12:33–41. https://doi.org/10.1080/15476278.2016.1145317 Dabi Y, Canel V, Skalli D, Paniel BJ, Haddad B, Touboul C (2020) Postoperative evaluation of chronic pain in patients with Mayer - Rokitansky - Küster - Hauser (MRKH) syndrome and uterine horn remnant: experience of a tertiary referring gynaecological department. J Gynecol Obstet Hum Reprod 49:101655. https://doi.org/10.1016/j.jogoh.2019.101655 Signorile PG, Baldi F, Bussani R, D’Armiento MR, De Falco M, Boccellino M et al (2010) New evidence sustaining the presence of endometriosis in the human foetus. Reprod Biomed Online 21:142–147 Signorile PG, Baldi A, Endometriosis: new concepts in the pathogenesis. Int J Bioch Cell Biol 42:778–870. https://doi.org/10.1016/j.biocel.2010.03.008 Browne H, Taylor H (2006) HOXA10 expression in ectopic endometrial tissue. Fertil Steril 85:1386–1390. https://doi.org/10.1016/j.fertnstert.2005.10.072 Matsuzaki S, Canis M, Darcha C, Pouly JL, Mage G (2009) HOXA-10 expression in the mid-secretory endometrium of infertile patients with either endometriosis, uterine fibromas or unexplained infertility. Hum Reprod (Oxford, England) 24:3180–3187. https://doi.org/10.1093/humrep/dep306 Gaetje R, Holtrich U, Engels K, Kissler S, Rody A, Karn T et al (2007) Endometriosis may be generated by mimicking the ontogenetic development of the female genital tract. Fertil Steril 87:651–656. https://doi.org/10.1016/j.fertnstert.2006.07.1533 Gaetje R, Holtrich U, Karn T, Cikrit E, Engels K, Rody A et al (2007) Characterization of WNT7A expression in human endometrium and endometriotic lesions. Fertil Steril 88:1534–1540. https://doi.org/10.1016/j.fertnstert.2007.01.128 de Mattos RM, Pereira PR, Barros EG, da Silva JH, Palmero CY, da Costa NM et al (2016) Aberrant levels of Wnt/β-catenin pathway components in a rat model of endometriosis. Histol Histopathol 31:933–942. https://doi.org/10.14670/hh-11-730 Xiong W, Zhang L, Yu L, Xie W, Man Y, Xiong Y et al (2015) Estradiol promotes cells invasion by activating β-catenin signaling pathway in endometriosis. Reproduction (Cambridge, England) 150:507–516. https://doi.org/10.1530/rep-15-0371 Zhang L, Xiong W, Xiong Y, Liu H, Liu Y (2016) 17 β-Estradiol promotes vascular endothelial growth factor expression via the Wnt/β-catenin pathway during the pathogenesis of endometriosis. Mol Hum Reprod 22:235–526. https://doi.org/10.1093/molehr/gaw025 Stewart B, Reddington C, Cameron M (2020) Laparoscopic hemihysterectomy for obstructive uterine didelphys with unilateral vaginal hypoplasia. J Minim Invasive Gynecol 27:1225–1227. https://doi.org/10.1016/j.jmig.2019.12.019 Fraunhoffer NA, Meilerman Abuelafia A, Stella I, Galliano S, Barrios M, Vitullo AD (2015) Identification of germ cell-specific VASA and IFITM3 proteins in human ovarian endometriosis. J Ovarian Res 8:66. https://doi.org/10.1186/s13048-015-0193-8 Simsek G, Bulus H, Tas A, Koklu S, Yilmaz SB, Coskun A (2012) An unusual cause of inguinal hernia in a male patient: endometriosis. Gut Liver 6:284–285. https://doi.org/10.5009/gnl.2012.6.2.284 Noë M, Ayhan A, Wang TL, Shih IM (2018) Independent development of endometrial epithelium and stroma within the same endometriosis. J Pathol 245:265–269. https://doi.org/10.1002/path.5082 Suda K, Nakaoka H, Yoshihara K, Ishiguro T, Tamura R, Mori Y et al (2018) Clonal expansion and diversification of cancer-associated mutations in endometriosis and normal endometrium. Cell Rep 24:1777–1789. https://doi.org/10.1016/j.celrep.2018.07.037 Jabbour HN, Kelly RW, Fraser HM, Critchley HO (2006) Endocrine regulation of menstruation. Endocr Rev 27:17–46. https://doi.org/10.1210/er.2004-0021 Tresserra F, Grases P, Ubeda A, Pascual MA, Grases PJ, Labastida R (1999) Morphological changes in hysterectomies after endometrial ablation. Hum Reprod (Oxford, England) 14:1473–1477. https://doi.org/10.1093/humrep/14.6.1473 Muller I, van der Palen J, Massop-Helmink D, Vos-de Bruin R, Sikkema JM (2015) Patient satisfaction and amenorrhea rate after endometrial ablation by ThermaChoice III or NovaSure: a retrospective cohort study. J Gynecol Surg 12:81–87 Cousins FL, Gargett CE (2018) Endometrial stem/progenitor cells and their role in the pathogenesis of endometriosis. Best Pract Res Clin Obstet Gynaecol 50:27–38. https://doi.org/10.1016/j.bpobgyn.2018.01.011 Tempest N, Maclean A, Hapangama DK (2018) Endometrial stem cell markers: current concepts and unresolved questions. Int J Mol Sci 19:3240. https://doi.org/10.3390/ijms19103240 Gargett CE, Masuda H (2010) Adult stem cells in the endometrium. Mol Hum Reprod 16:818–834. https://doi.org/10.1093/molehr/gaq061 Schwab KE, Gargett CE (2007) Co-expression of two perivascular cell markers isolates mesenchymal stem-like cells from human endometrium. Hum Reprod (Oxford, England). 22:2903–2911. https://doi.org/10.1093/humrep/dem265 Masuda H, Anwar SS, Bühring HJ, Rao JR, Gargett CE (2012) A novel marker of human endometrial mesenchymal stem-like cells. Cell Transplant 21:2201–2214. https://doi.org/10.3727/096368911x637362 Chan RW, Schwab KE, Gargett CE (2004) Clonogenicity of human endometrial epithelial and stromal cells. Biol Reprod 70:1738–1750. https://doi.org/10.1095/biolreprod.103.024109 Nguyen HPT, Xiao L, Deane JA, Tan KS, Cousins FL, Masuda H et al (2017) N-cadherin identifies human endometrial epithelial progenitor cells by in vitro stem cell assays. Hum Reprod (Oxford, England). 32:2254–2268. https://doi.org/10.1093/humrep/dex289 Masuda H, Matsuzaki Y, Hiratsu E, Ono M, Nagashima T, Kajitani T et al (2010) Stem cell-like properties of the endometrial side population: implication in endometrial regeneration. PLoS ONE 5:e10387. https://doi.org/10.1371/journal.pone.0010387 Miyazaki K, Maruyama T, Masuda H, Yamasaki A, Uchida S, Oda H et al (2012) Stem cell-like differentiation potentials of endometrial side population cells as revealed by a newly developed in vivo endometrial stem cell assay. PLoS ONE 7:e50749. https://doi.org/10.1371/journal.pone.0050749 Goodell MA, Rosenzweig M, Kim H, Marks DF, DeMaria M, Paradis G et al (1997) Dye efflux studies suggest that hematopoietic stem cells expressing low or undetectable levels of CD34 antigen exist in multiple species. Nat Med 3:1337–1345. https://doi.org/10.1038/nm1297-1337 Gurung S, Deane JA, Masuda H, Maruyama T, Gargett CE (2015) Stem cells in endometrial physiology. Semin Reprod Med 33:326–332. https://doi.org/10.1055/s-0035-1558405 Cervelló I, Mas A, Gil-Sanchis C, Peris L, Faus A, Saunders PT et al (2011) Reconstruction of endometrium from human endometrial side population cell lines. PLoS ONE 6:e21221. https://doi.org/10.1371/journal.pone.0021221 Leyendecker G, Herbertz M, Kunz G, Mall G (2002) Endometriosis results from the dislocation of basal endometrium. Hum Reprod (Oxford, England) 17:2725–2736. https://doi.org/10.1093/humrep/17.10.2725 Hapangama DK, Drury J, Da Silva L, Al-Lamee H, Earp A, Valentijn AJ et al (2019) Abnormally located SSEA1+/SOX9+ endometrial epithelial cells with a basalis-like phenotype in the eutopic functionalis layer may play a role in the pathogenesis of endometriosis. Hum Reprod (Oxford, England) 34:56–68. https://doi.org/10.1093/humrep/dey336 Valentijn AJ, Palial K, Al-Lamee H, Tempest N, Drury J, Von Zglinicki T et al (2013) SSEA-1 isolates human endometrial basal glandular epithelial cells: phenotypic and functional characterization and implications in the pathogenesis of endometriosis. Hum Reprod (Oxford, England) 28:2695–2708. https://doi.org/10.1093/humrep/det285 Kao AP, Wang KH, Chang CC, Lee JN, Long CY, Chen HS et al (2011) Comparative study of human eutopic and ectopic endometrial mesenchymal stem cells and the development of an in vivo endometriotic invasion model. Fertil Steril 95:1308–1315.e1. https://doi.org/10.1016/j.fertnstert.2010.09.064 Tempest N, Baker AM, Wright NA, Hapangama DK (2018) Does human endometrial LGR5 gene expression suggest the existence of another hormonally regulated epithelial stem cell niche? Hum Reprod (Oxford, England) 33:1052–1062. https://doi.org/10.1093/humrep/dey083 Leyendecker G, Kunz G, Herbertz M, Beil D, Huppert P, Mall G et al (2004) Uterine peristaltic activity and the development of endometriosis. Ann N Y Acad Sci 1034:338–355. https://doi.org/10.1196/annals.1335.036 Vercellini P, Viganò P, Somigliana E, Fedele L (2014) Endometriosis: pathogenesis and treatment. Nat Rev Endocrinol 10:261–275. https://doi.org/10.1038/nrendo.2013.255 Guo SW (2009) Recurrence of endometriosis and its control. Hum Reprod Update 15:441–461. https://doi.org/10.1093/humupd/dmp007 Gordts S, Koninckx P, Brosens I (2017) Pathogenesis of deep endometriosis. Fertil Steril 108:285–872.e1. https://doi.org/10.1016/j.fertnstert.2017.08.036 Chan RW, Ng EH, Yeung WS (2011) Identification of cells with colony-forming activity, self-renewal capacity, and multipotency in ovarian endometriosis. Am J Pathol 178:2832–2844. https://doi.org/10.1016/j.ajpath.2011.02.025 Liu Y, Liang S, Yang F, Sun Y, Niu L, Ren Y et al (2020) Biological characteristics of endometriotic mesenchymal stem cells isolated from ectopic lesions of patients with endometriosis. Stem Cell Res Ther 11:346. https://doi.org/10.1186/s13287-020-01856-8 Chang JH, Au HK, Lee WC, Chi CC, Ling TY, Wang LM et al (2013) Expression of the pluripotent transcription factor OCT4 promotes cell migration in endometriosis. Fertil Steril 99:1332–1339.e5. https://doi.org/10.1016/j.fertnstert.2012.11.033 Zhang Y, Eades G, Yao Y, Li Q, Zhou Q (2012) Estrogen receptor α signaling regulates breast tumor-initiating cells by down-regulating miR-140 which targets the transcription factor SOX2. J Biol Chem 287:41514–41522. https://doi.org/10.1074/jbc.M112.404871 Yang L, Luo L, Ji W, Gong C, Wu D, Huang H et al (2013) Effect of low dose bisphenol A on the early differentiation of human embryonic stem cells into mammary epithelial cells. Toxicol Lett 218:187–193. https://doi.org/10.1016/j.toxlet.2013.01.026 Banerjee P, Fazleabas AT (2010) Endometrial responses to embryonic signals in the primate. Int J Dev Biol 54:295–302. https://doi.org/10.1387/ijdb.082829pb Bray SJ (2006) Notch signalling: a simple pathway becomes complex. Nature Rev Mol Cell Biol 7:678–689. https://doi.org/10.1038/nrm2009 He H, Liu R, Xiong W, Pu D, Wang S, Li T (2016) Lentiviral vector-mediated down-regulation of Notch1 in endometrial stem cells results in proliferation and migration in endometriosis. Mol Cell Endocrinol 434:210–218. https://doi.org/10.1016/j.mce.2016.07.004 Götte M, Wolf M, Staebler A, Buchweitz O, Kelsch R, Schüring AN et al (2008) Increased expression of the adult stem cell marker Musashi-1 in endometriosis and endometrial carcinoma. J Pathol 215:317–329. https://doi.org/10.1002/path.2364 Li X, Gong X, Zhu L, Leng J, Fan Q, Sun D et al (2012) Stretch magnitude- and frequency-dependent cyclooxygenase 2 and prostaglandin E2 up-regulation in human endometrial stromal cells: possible implications in endometriosis. Exp Biol Med (Maywood, NJ) 237:1350–1358. https://doi.org/10.1258/ebm.2012.012060 Sha G, Zhang Y, Zhang C, Wan Y, Zhao Z, Li C et al (2009) Elevated levels of gremlin-1 in eutopic endometrium and peripheral serum in patients with endometriosis. Fertil Sterilit 91:350–358. https://doi.org/10.1016/j.fertnstert.2007.12.007 Treloar SA, O’Connor DT, O’Connor VM, Martin NG (1999) Genetic influences on endometriosis in an Australian twin sample. Fertil Steril 71:701–710. https://doi.org/10.1016/s0015-0282(98)00540-8 Guo SW (2020) Cancer-associated mutations in endometriosis: shedding light on the pathogenesis and pathophysiology. Hum Reprod Update 26:423–449. https://doi.org/10.1093/humupd/dmz047 Lac V, Nazeran TM, Tessier-Cloutier B, Aguirre-Hernandez R, Albert A, Lum A et al (2019) Oncogenic mutations in histologically normal endometrium: the new normal? J Pathol 249:173–181. https://doi.org/10.1002/path.5314 Araten DJ, Golde DW, Zhang RH, Thaler HT, Gargiulo L, Notaro R et al (2005) A quantitative measurement of the human somatic mutation rate. Cancer Res 65:8111–8117. https://doi.org/10.1158/0008-5472.can-04-1198 Nachman MW, Crowell SL (2000) Estimate of the mutation rate per nucleotide in humans. Genetics 156:297–304 Rozhok AI, DeGregori J (2016) The evolution of lifespan and age-dependent cancer risk. Trends Cancer 2:552–560. https://doi.org/10.1016/j.trecan.2016.09.004 Moore L, Leongamornlert D, Coorens THH, Sanders MA, Ellis P, Dentro SC et al (2020) The mutational landscape of normal human endometrial epithelium. Nature 580:640–646. https://doi.org/10.1038/s41586-020-2214-z Cheng CW, Licence D, Cook E, Luo F, Arends MJ, Smith SK et al (2011) Activation of mutated K-ras in donor endometrial epithelium and stroma promotes lesion growth in an intact immunocompetent murine model of endometriosis. J Pathol 224:261–269. https://doi.org/10.1002/path.2852 Wu RC, Wang TL, Shih Ie M (2014) The emerging roles of ARID1A in tumor suppression. Cancer Biol Ther 15:655–664. https://doi.org/10.4161/cbt.28411 Anglesio MS, Papadopoulos N, Ayhan A, Nazeran TM, Noë M, Horlings HM et al (2017) Cancer-associated mutations in endometriosis without cancer. N Engl J Med 376:1835–1848. https://doi.org/10.1056/NEJMoa1614814 Kandoth C, Schultz N, Cherniack AD, Akbani R, Liu Y, Shen H et al (2013) Integrated genomic characterization of endometrial carcinoma. Nature 497:67–73. https://doi.org/10.1038/nature12113 Ma Y, Huang YX, Chen YY (2017) miRNA-34a-5p downregulation of VEGFA in endometrial stem cells contributes to the pathogenesis of endometriosis. Mol Med Rep 16:8259–8264. https://doi.org/10.3892/mmr.2017.7677 Lai CY, Yamazaki S, Okabe M, Suzuki S, Maeyama Y, Iimura Y et al (2014) Stage-specific roles for CXCR4 signaling in murine hematopoietic stem/progenitor cells in the process of bone marrow repopulation. Stem Cells (Dayton, Ohio) 32:1929–1942. https://doi.org/10.1002/stem.1670 Hattori K, Heissig B, Rafii S (2003) The regulation of hematopoietic stem cell and progenitor mobilization by chemokine SDF-1. Leuk Lymphoma 44:575–582. https://doi.org/10.1080/1042819021000037985 Leconte M, Chouzenoux S, Nicco C, Chéreau C, Arkwright S, Santulli P et al (2014) Role of the CXCL12-CXCR4 axis in the development of deep rectal endometriosis. J Reprod Immunol 103:45–52. https://doi.org/10.1016/j.jri.2013.12.121 Moridi I, Mamillapalli R, Cosar E, Ersoy GS, Taylor HS (2017) Bone marrow stem cell chemotactic activity is induced by elevated CXCl12 in endometriosis. Reprod Sci (Thousand Oaks, Calif). 24:526–533. https://doi.org/10.1177/1933719116672587 Pospisilova E, Kiss I, Souckova H, Tomes P, Spicka J, Matkowski R et al (2019) Circulating endometrial cells: a new source of information on endometriosis dynamics. J Clin Med 8:1938. https://doi.org/10.3390/jcm8111938

The authors are grateful to Dr. Bayan Alsaid for assisting in designing Fig. 9.1. Author information Authors and Affiliations Corresponding author Editor information Editors and Affiliations Rights and permissions Copyright information © 2022 The Author(s), under exclusive license to Springer Nature Switzerland AG About this chapter Cite this chapter Laganà, A.S., Naem, A. (2022). The Pathogenesis of Endometriosis: Are Endometrial Stem/Progenitor Cells Involved?. In: Virant-Klun, I. (eds) Stem Cells in Reproductive Tissues and Organs. Stem Cell Biology and Regenerative Medicine, vol 70. Humana, Cham. https://doi.org/10.1007/978-3-030-90111-0_9 Download citation DOI: https://doi.org/10.1007/978-3-030-90111-0_9 Published: Publisher Name: Humana, Cham Print ISBN: 978-3-030-90110-3 Online ISBN: 978-3-030-90111-0 eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)