Journal of Shandong University (Health Sciences) ›› 2019, Vol. 57 ›› Issue (6): 33-39.doi: 10.6040/j.issn.1671-7554.0.2019.521

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Research advances in the pathogenesis of endometriosis

WANG Guoyun, YUAN Ming, JI Miaomiao   

  1. Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan 250012, Shandong, China)Abstract: Endometriosis(EMs)is a common gynecological disease with a prevalence of 10% in women of childbearing age. The main symptoms of EMs are pain and infertility, which seriously affect patients quality of life. However, 〓山〓东〓大〓学〓学〓报〓(医〓学〓版)57卷6期〓-王国云, 等.子宫内膜异位症发病机制研究进展〓\=-
  • Published:2022-09-27

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Abstract: Endometriosis(EMs)is a common gynecological disease with a prevalence of 10% in women of childbearing age. The main symptoms of EMs are pain and infertility, which seriously affect patients quality of life. However, 山 东 大 学 学 报 (医 学 版)57卷6期 -王国云,等.子宫内膜异位症发病机制研究进展 \=- there is no EMs-specific, non-invasive diagnostic method yet. Currently, EMs is treated with surgery or hormonoth-erapy, both of which have side effects and high recurrence rate. The ambiguity of EMs pathogenesis limits the diagnosis and treatment. The mainstream theory is retrograde menstruation, but the latest research shows that EMS is a complex chronic disease, which may be induced by the menstrual blood flow, while the complex interaction between genetic, immune and environmental factors plays a more important role. This paper will review the pathogenesis theories and latest research advances, especially the new research fields of EMs, and propose the problems in the EMs mechanism research.

Key words: Endometriosis, Gene, Immunity, Gut microbiota, Exosome

CLC Number: 

  • R711.71
[1] Giudice LC. Clinical practice. Endometriosis[J]. N Engl J Med, 2010, 362(25): 2389-2398.
[2] Vercellini P, Viganò P, Somigliana E, et al. Endometriosis: pathogenesis and treatment[J]. Nat Rev Endocrinol, 2014, 10(5): 261-275.
[3] Zondervan KT, Becker CM, Koga K, et al. Endometriosis[J]. Nat Rev Dis Primers, 2018, 4(1): 9. doi: 10.1038/s41572-018-0008-5.
[4] Symons LK, Miller JE, Kay VR, et al. The immunopathophysiology of endometriosis[J]. Trends Mol Med, 2018, 24(9): 748-762.
[5] Sampson JA. Metastatic or Embolic endometriosis, due to the Menstrual Dissemination of Endometrial Tissue into the Venous Circulation[J]. Am J Pathol, 1927, 3(2): 93-110.
[6] Missmer SA, Hankinson SE, Spiegelman D, et al. Reproductive history and endometriosis among premenopausal women[J]. Obstet Gynecol, 2004, 104(5 Pt 1): 965-974.
[7] Vercellini P, Abbiati A, Viganò P, et al. Asymmetry in distribution of diaphragmatic endometriotic lesions: evidence in favour of the menstrual reflux theory[J]. Hum Reprod, 2007, 22(9): 2359-2367.
[8] DHooghe TM, Bambra CS, Raeymaekers BM, et al. Increased prevalence and recurrence of retrograde menstruation in baboons with spontaneous endometriosis[J]. Hum Reprod, 1996, 11(9): 2022-2025.
[9] Witz CA, Cho S, Centonze VE, et al. Time series analysis of transmesothelial invasion by endometrial stromal and epithelial cells using three-dimensional confocal microscopy[J]. Fertil Steril, 2003, 79(Suppl 1): 770-778.
[10] Sanchez AM, Viganò P, Somigliana E, et al. The endometriotic tissue lining the internal surface of endometrioma: hormonal, genetic, epigenetic status, and gene expression profile[J]. Reprod Sci, 2015, 22(4): 391-401.
[11] Ferguson BR, Bennington JL, Haber SL. Histochemistry of mucosubstances and histology of mixed müllerian pelvic lymph node glandular inclusions. Evidence for histogenesis by müllerian metaplasia of coelomic epithelium[J]. Obstet Gynecol, 1969, 33(5): 617-625.
[12] Du HL, Taylor HS. Contribution of bone marrow-derived stem cells to endometrium and endometriosis[J]. Stem Cells, 2007, 25(8): 2082-2086.
[13] Gargett CE, Masuda H. Adult stem cells in the endometrium[J]. Mol Hum Reprod, 2010, 16(11): 818-834.
[14] Mechsner S, Weichbrodt M, Riedlinger WF, et al. Estrogen and progestogen receptor positive endometriotic lesions and disseminated cells in pelvic sentinel lymph nodes of patients with deep infiltrating rectovaginal endometriosis: a pilot study[J]. Hum Reprod, 2008, 23(10): 2202-2209.
[15] Gargett CE, Schwab KE, Brosens JJ, et al. Potential role of endometrial stem/progenitor cells in the pathogenesis of early-onset endometriosis[J]. Mol Hum Reprod, 2014, 20(7): 591-598.
[16] Treloar SA, Wicks J, Nyholt DR, et al. Genomewide linkage study in 1, 176 affected sister pair families identifies a significant susceptibility locus for endometriosis on chromosome 10q26[J]. Am J Hum Genet, 2005, 77(3): 365-376.
[17] Zondervan KT, Treloar SA, Lin JH, et al. Significant evidence of one or more susceptibility loci for endometriosis with near-Mendelian inheritance on chromosome 7p13-15[J]. Hum Reprod, 2007, 22(3): 717-728.
[18] Sapkota Y, Steinthorsdottir V, Morris AP, et al. Meta-analysis identifies five novel loci associated with endometriosis highlighting key genes involved in hormone metabolism[J]. Nat Commun, 2017, 8: 15539. doi:10.1038/ncomms15539.
[19] Anglesio MS, Papadopoulos N, Ayhan A, et al. Cancer-associated mutations in endometriosis without cancer[J]. N Engl J Med, 2017, 376(19): 1835-1848.
[20] Li XL, Zhang Y, Zhao LY, et al. Whole-exome sequencing of endometriosis identifies frequent alterations in genes involved in cell adhesion and chromatin-remodeling complexes[J]. Hum Mol Genet, 2014, 23(22): 6008-6021.
[21] Suda K, Nakaoka H, Yoshihara K, et al. Clonal expansion and diversification of cancer-associated mutations in endometriosis and normal endometrium[J]. Cell Rep, 2018, 24(7): 1777-1789.
[22] Borghese B, Zondervan KT, Abrao MS, et al. Recent insights on the genetics and epigenetics of endometriosis[J]. Clin Genet, 2017, 91(2): 254-264.
[23] Dyson MT, Roqueiro D, Monsivais D, et al. Genome-wide DNA methylation analysis predicts an epigenetic switch for GATA factor expression in endometriosis[J]. PLoS Genet, 2014, 10(3): e1004158.
[24] Burney RO, Hamilton AE, Aghajanova L, et al. MicroRNA expression profiling of eutopic secretory endometrium in women with versus without endometriosis[J]. Mol Hum Reprod, 2009, 15(10): 625-631.
[25] Lin YJ, Lai MD, Lei HY, et al. Neutrophils and macrophages promote angiogenesis in the early stage of endometriosis in a mouse model[J]. Endocrinology, 2006, 147(3): 1278-1286.
[26] Takamura M, Koga K, Izumi G, et al. Neutrophil depletion reduces endometriotic lesion formation in mice[J]. Am J Reprod Immunol, 2016, 76(3): 193-198.
[27] Capobianco A, Rovere-Querini P. Endometriosis, a disease of the macrophage[J]. Front Immunol, 2013, 14(1): 53.
[28] Berbic M, Schulke L, Markham R, et al. Macrophage expression in endometrium of women with and without endometriosis[J]. Hum Reprod, 2009, 24(2): 325-332.
[29] Chuang PC, Wu MH, Shoji Y, et al. Downregulation of CD36 results in reduced phagocytic ability of peritoneal macrophages of women with endometriosis[J]. J Pathol, 2009, 219(2): 232-241.
[30] Chuang PC, Lin YJ, Wu MH, et al. Inhibition of CD36-dependent phagocytosis by prostaglandin E2 contributes to the development of endometriosis[J]. Am J Pathol, 2010, 176(2): 850-860.
[31] Lousse JC, Van Langendonckt A, González-Ramos R, et al. Increased activation of nuclear factor-kappa B(NF-kappaB)in isolated peritoneal macrophages of patients with endometriosis[J]. Fertil Steril, 2008, 90(1): 217-220.
[32] Chan RWS, Lee CL, Ng EHY, et al. Co-culture with macrophages enhances the clonogenic and invasion activity of endometriotic stromal cells[J]. Cell Prolif, 2017, 50(3). doi: 10.1111/cpr.12330.
[33] Shao J, Zhang B, Yu JJ, et al. Macrophages promote the growth and invasion of endometrial stromal cells by downregulating IL-24 in endometriosis[J]. Reproduction, 2016, 152(6): 673-682.
[34] Tran LV, Tokushige N, Berbic M, et al. Macrophages and nerve fibres in peritoneal endometriosis[J]. Hum Reprod, 2009, 24(4): 835-841.
[35] Greaves E, Temp J, Esnal-Zufiurre A, et al. Estradiol is a critical mediator of macrophage-nerve cross talk in peritoneal endometriosis[J]. Am J Pathol, 2015, 185(8): 2286-2297.
[36] Bacci M, Capobianco A, Monno A, et al. Macrophages are alternatively activated in patients with endometriosis and required for growth and vascularization of lesions in a mouse model of disease[J]. Am J Pathol, 2009, 175(2): 547-556.
[37] Itoh F, Komohara Y, Takaishi K, et al. Possible involvement of signal transducer and activator of transcription-3 in cell-cell interactions of peritoneal macrophages and endometrial stromal cells in human endometriosis[J]. Fertil Steril, 2013, 99(6): 1705-1713.
[38] Beste MT, Pfäffle DN, Prentice EA, et al. Molecular network analysis of endometriosis reveals a role for c-Jun-regulated macrophage activation[J]. Sci Transl Med, 2014, 6(222): 222ra16. doi: 10.1126/scitranslmed.3007988.
[39] Yuan M, Li D, An M, et al. Rediscovering peritoneal macrophages in a murine endometriosis model[J]. Hum Reprod, 2017, 32(1): 94-102.
[40] Oosterlynck DJ, Meuleman C, Waer M, et al. Immunosuppressive activity of peritoneal fluid in women with endometriosis[J]. Obstet Gynecol, 1993, 82(2): 206-212.
[41] González-Foruria I, Santulli P, Chouzenoux S, et al. Soluble ligands for the NKG2D receptor are released during endometriosis and correlate with disease severity[J]. PLoS One, 2015, 10(3): e0119961.
[42] Matsuoka S, Maeda N, Izumiya C, et al. Expression of inhibitory-motif killer immunoglobulin-like receptor, KIR2DL1, is increased in natural killer cells from women with pelvic endometriosis[J]. Am J Reprod Immunol, 2005, 53(5): 249-254.
[43] Kang YJ, Jeung IC, Park A, et al. An increased level of IL-6 suppresses NK cell activity in peritoneal fluid of patients with endometriosis via regulation of SHP-2 expression[J]. Hum Reprod, 2014, 29(10): 2176-2189.
[44] Guo SW, Du YB, Liu XS. Platelet-derived TGF-β1 mediates the down-modulation of NKG2D expression and may be responsible for impaired natural killer(NK)cytotoxicity in women with endometriosis[J]. Hum Reprod, 2016, 31(7): 1462-1474.
[45] Yu JJ, Sun HT, Zhang ZF, et al. IL15 promotes growth and invasion of endometrial stromal cells and inhibits killing activity of NK cells in endometriosis[J]. Reproduction, 2016, 152(2): 151-160.
[46] Podgaec S, Abrao MS, Dias JA Jr, et al. Endometriosis: an inflammatory disease with a Th2 immune response component[J]. Hum Reprod, 2007, 22(5): 1373-1379.
[47] Gogacz M, Winkler I, Bojarska-Junak A, et al. Increased percentage of Th17 cells in peritoneal fluid is associated with severity of endometriosis[J]. J Reprod Immunol, 2016, 117: 39-44. doi:10.1016/j.jri.2016.04.289.
[48] de Barros IBL, Malvezzi H, Gueuvoghlanian-Silva BY, et al. “What do we know about regulatory T cells and endometriosis? A systematic review”[J]. J Reprod Immunol, 2017, 120: 48-55. doi:10.1016/j.jri.2017.04.003.
[49] Bulun SE, Yilmaz BD, Sison C, et al. Endometriosis[J]. Endocrine Reviews, 2019: pii: er.2018-00242. doi: 10.1210/er.2018-00242.
[50] Laschke MW, Menger MD. Basic mechanisms of vascularization in endometriosis and their clinical implications[J]. Hum Reprod Update, 2018. doi: 10.1093/humupd/dmy001.
[51] Schjenken JE, Panir K, Robertson SA, et al. Exosome-mediated intracellular signalling impacts the development of endometriosis-new avenues for endometriosis research[J]. Mol Hum Reprod, 2019, 25(1): 2-4.
[52] Harp D, Driss A, Mehrabi S, et al. Exosomes derived from endometriotic stromal cells have enhanced angiogenic effects in vitro[J]. Cell Tissue Res, 2016, 365(1): 187-196.
[53] Sun HH, Li D, Yuan M, et al. Eutopic stromal cells of endometriosis promote neuroangiogenesis via exosome pathway[J]. Biol Reprod, 2019, 100(3): 649-659.
[54] Zhang AF, Wang GY, Jia LH, et al. Exosome-mediated microRNA-138 and vascular endothelial growth factor in endometriosis through inflammation and apoptosis via the nuclear factor-κB signaling pathway[J]. Int J Mol Med, 2019, 43(1): 358-370.
[55] Qiu JJ, Lin XJ, Zheng TT, et al. The exosomal long noncoding RNA aHIF is upregulated in serum from patients with endometriosis and promotes angiogenesis in endometriosis[J]. Reprod Sci, 2019: 1933719119831775. doi: 10.1177/1933719119831775.
[56] Laschke MW, Menger MD. The gut microbiota: a puppet master in the pathogenesis of endometriosis?[J]. Am J Obstet Gynecol, 2016, 215(1): 68.e1-e4.
[57] Bailey MT, Coe CL. Endometriosis is associated with an altered profile of intestinal microflora in female rhesus monkeys[J]. Hum Reprod, 2002, 17(7): 1704-1708.
[58] Yuan M, Li D, Zhang Z, et al. Endometriosis induces gut microbiota alterations in mice[J]. Hum Reprod, 2018, 33(4): 607-616.
[59] Vétizou M, Pitt JM, Daillère R, et al. Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota[J]. Science, 2015, 350(6264): 1079-1084.
[60] Sivan A, Corrales L, Hubert N, et al. Commensal Bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy[J]. Science, 2015, 350(6264): 1084-1089.
[61] Chadchan SB, Cheng M, Parnell LA, et al. Antibiotic therapy with metronidazole reduces endometriosis disease progression in mice: a potential role for gut microbiota[J]. Hum Reprod, 2019, 34(6):1106-1116.
[62] Wu L, Lv C, Su YF, et al. Expression of programmed death-1(PD-1)and its ligand PD-L1 is upregulated in endometriosis and promoted by 17beta-estradiol[J]. Gynecological Endocrinology, 2019, 35(3): 251-256.
[63] Walankiewicz M, Grywalska E, Polak G, et al. The increase of circulating PD-1- and PD-L1-expressing lymphocytes in endometriosis: correlation with clinical and laboratory parameters[J]. Mediators Inflamm, 2018, 2018: 7041342. doi: 10.1155/2018/7041342.
[64] Xie Q, He H, Wu YH, et al. Eutopic endometrium from patients with endometriosis modulates the expression of CD36 and SIRP-α in peritoneal macrophages[J]. J Obstet Gynaecol Res, 2019, 45(5): 1045-1057.
[65] Bellofiore N, Ellery SJ, Mamrot J, et al. First evidence of a menstruating rodent: the spiny mouse(Acomys cahirinus)[J]. Am J Obstet Gynecol, 2017, 216(1): 40.e41-40.e11.
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