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Gene Expression in Endometriosis

  • Niraj Joshi
  • Ren-Wei Su
  • Asgerally FazleabasEmail author
Chapter

Abstract

Endometriosis is a common gynecological disorder defined by the presence of endometrial tissue outside the uterus which affects 10–15% of women and is associated with pelvic pain and infertility. It is an estrogen-dependent, inflammatory disease associated with elevated tissue, peripheral and peritoneal cytokines. The presence of the disease results in aberrant gene expression in the eutopic endometrium, development of progesterone resistance, and impaired decidualization. The molecular mechanisms driving these phenotypic changes in both the eutopic and ectopic endometrium are not clear. Therefore, to study the mechanisms of disease onset and early development, animal models in which the onset of disease can be exactly controlled are necessary. The use of nonhuman primates is advantageous for the study of endometriosis because they are phylogenetically similar to humans. Among all the available nonhuman primate models, the baboon (Papio anubis) is preferred because of its size, similar reproductive anatomy and physiology, and the ability to evaluate disease pathogenesis from the onset of disease induction. This chapter summarizes our findings on how the presence of ectopic lesions influences the eutopic endometrial gene signature leading to altered endometrial function, progesterone resistance, and impaired decidualization. We suggest that the presence of endometriosis leads to rapid and significant changes in the expression of several microRNAs (miRNAs) which in turn may impact the altered gene signature contributing to the pathology of the disease including progesterone resistance. Notch signaling plays a vital role in cell survival, cellular communication, and differentiation throughout development in a variety of species. We document that decreased NOTCH1 signaling in eutopic endometrium compromises decidualization. Additionally, we demonstrate that altered signaling pathways (AKT, MAPK, ERK, and HIF1A-STAT3) along with epigenetic changes further contribute to progesterone resistance and decidualization defects. Thus, inflammation and altered microRNA expression, in both the eutopic and ectopic endometrium, impact the progesterone-regulated gene networks leading to compromised endometrial function as a consequence of endometriosis.

Keywords

Endometriosis Progesterone resistance Decidualization microRNA Gene expression 

Notes

Acknowledgments

Portions of this research were supported by grants from the Eunice Kennedy Shriver NICHD R01-HD083273 and R01-HD042280 to Prof. Asgerally Fazleabas and SRI-Bayer Discovery grant to Dr. Niraj Joshi. The authors would like to thank the members of Fazleabas Laboratory at Michigan State University for their support in carrying out these experiments.

References

  1. 1.
    Braundmeier AG, Fazleabas AT. The non-human primate model of endometriosis: research and implications for fecundity. Mol Hum Reprod. 2009;15(10):577–86.PubMedPubMedCentralCrossRefGoogle Scholar
  2. 2.
    Giudice LC, Kao LC. Endometriosis Lancet. 2004;364(9447):1789–99.PubMedCrossRefPubMedCentralGoogle Scholar
  3. 3.
    Eskenazi B, Warner ML. Epidemiology of endometriosis. Obstet Gynecol Clin North Am. 1997;24(2):235–58.PubMedCrossRefGoogle Scholar
  4. 4.
    Chapron C, Bourret A, Chopin N, Dousset B, Leconte M, Amsellem-Ouazana D, et al. Surgery for bladder endometriosis: long-term results and concomitant management of associated posterior deep lesions. Hum Reprod. 2010;25(4):884–9.PubMedCrossRefGoogle Scholar
  5. 5.
    Giudice LC. Clinical practice. Endometriosis. N Engl J Med. 2010;362(25):2389–98.PubMedPubMedCentralCrossRefGoogle Scholar
  6. 6.
    Bulun SE. Endometriosis. N Engl J Med. 2009;360(3):268–79.PubMedCrossRefGoogle Scholar
  7. 7.
    Missmer SA, Hankinson SE, Spiegelman D, Barbieri RL, Marshall LM, Hunter DJ. Incidence of laparoscopically confirmed endometriosis by demographic, anthropometric, and lifestyle factors. Am J Epidemiol. 2004;160(8):784–96.PubMedCrossRefGoogle Scholar
  8. 8.
    Sampson JA. Peritoneal endometriosis, due to the menstrual dissemination of endometrial tissue into the peritoneal cavity. Am J Obstet Gynecol. 1927;15(1):101–10.Google Scholar
  9. 9.
    D’Hooghe TM. Clinical relevance of the baboon as a model for the study of endometriosis. Fertil Steril. 1997;68(4):613–25.PubMedCrossRefGoogle Scholar
  10. 10.
    Hastings JM, Fazleabas AT. A baboon model for endometriosis: implications for fertility. Reprod Biol Endocrinol. 2006;4 Suppl 1:S7.Google Scholar
  11. 11.
    McKinnon BD, Bertschi D, Wanner J, Bersinger NA, Mueller MD. Hormonal contraceptive use and the prevalence of endometriotic lesions at different regions within the peritoneal cavity. Biomed Res Int. 2014;2014:590950.PubMedPubMedCentralCrossRefGoogle Scholar
  12. 12.
    Ruiz A, Ruiz L, Colon-Caraballo M, Torres-Collazo BJ, Monteiro JB, Bayona M, et al. Pharmacological blockage of the CXCR4-CXCL12 axis in endometriosis leads to contrasting effects in proliferation, migration, and invasion. Biol Reprod. 2018;98(1):4–14.PubMedCrossRefGoogle Scholar
  13. 13.
    Hapangama DK, Drury J, Da Silva L, Al-Lamee H, Earp A, Valentijn AJ, et al. 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. 2019;34(1):56–68.PubMedCrossRefGoogle Scholar
  14. 14.
    Du H, Taylor HS. Contribution of bone marrow-derived stem cells to endometrium and endometriosis. Stem Cells. 2007;25(8):2082–6.PubMedCrossRefGoogle Scholar
  15. 15.
    Gargett CE, Schwab KE, Deane JA. Endometrial stem/progenitor cells: the first 10 years. Hum Reprod Update. 2016;22(2):137–63.PubMedGoogle Scholar
  16. 16.
    Elliott JE, Abduljabar H, Morris M. Presurgical management of dysmenorrhea and endometriosis in a patient with Mayer-Rokitansky-Kuster-Hauser syndrome. Fertil Steril. 2011;96(2):e86–9.PubMedCrossRefGoogle Scholar
  17. 17.
    Matsuura K, Ohtake H, Katabuchi H, Okamura H. Coelomic metaplasia theory of endometriosis: evidence from in vivo studies and an in vitro experimental model. Gynecol Obstet Invest. 1999;47 Suppl 1:18–20; discussion 20–2.PubMedCrossRefGoogle Scholar
  18. 18.
    Nisolle M, Donnez J. Peritoneal endometriosis, ovarian endometriosis, and adenomyotic nodules of the rectovaginal septum are three different entities. Fertil Steril. 1997;68(4):585–96.PubMedCrossRefGoogle Scholar
  19. 19.
    Fazleabas AT, Brudney A, Gurates B, Chai D, Bulun S. A modified baboon model for endometriosis. Ann N Y Acad Sci. 2002;955:308–17; discussion 40–2, 96–406PubMedCrossRefGoogle Scholar
  20. 20.
    Nishimoto-Kakiuchi A, Netsu S, Matsuo S, Hayashi S, Ito T, Okabayashi S, et al. Characteristics of histologically confirmed endometriosis in cynomolgus monkeys. Hum Reprod. 2016;31(10):2352–9.PubMedPubMedCentralCrossRefGoogle Scholar
  21. 21.
    Ami Y, Suzaki Y, Goto N. Endometriosis in cynomolgus monkeys retired from breeding. J Vet Med Sci. 1993;55(1):7–11.PubMedCrossRefPubMedCentralGoogle Scholar
  22. 22.
    Zondervan K, Cardon L, Desrosiers R, Hyde D, Kemnitz J, Mansfield K, et al. The genetic epidemiology of spontaneous endometriosis in the rhesus monkey. Ann N Y Acad Sci. 2002;955:233–8; discussion 93–5, 396–406.PubMedCrossRefGoogle Scholar
  23. 23.
    Schenken RS, Asch RH, Williams RF, Hodgen GD. Etiology of infertility in monkeys with endometriosis: measurement of peritoneal fluid prostaglandins. Am J Obstet Gynecol. 1984;150(4):349–53.PubMedCrossRefGoogle Scholar
  24. 24.
    Einspanier A, Lieder K, Bruns A, Husen B, Thole H, Simon C. Induction of endometriosis in the marmoset monkey (Callithrix jacchus). Mol Hum Reprod. 2006;12(5):291–9.PubMedCrossRefGoogle Scholar
  25. 25.
    Fazleabas AT. A baboon model for inducing endometriosis. Methods Mol Med. 2006;121:95–9.PubMedGoogle Scholar
  26. 26.
    D’Hooghe TM, Kyama CM, Chai D, Fassbender A, Vodolazkaia A, Bokor A, et al. Nonhuman primate models for translational research in endometriosis. Reprod Sci. 2009;16(2):152–61.PubMedCrossRefGoogle Scholar
  27. 27.
    D'Hooghe TM, Bambra CS, Raeymaekers BM, De Jonge I, Lauweryns JM, Koninckx PR. Intrapelvic injection of menstrual endometrium causes endometriosis in baboons (Papio cynocephalus and Papio anubis). Am J Obstet Gynecol. 1995;173(1):125–34.PubMedCrossRefGoogle Scholar
  28. 28.
    Harirchian P, Gashaw I, Lipskind ST, Braundmeier AG, Hastings JM, Olson MR, et al. Lesion kinetics in a non-human primate model of endometriosis. Hum Reprod. 2012;27(8):2341–51.PubMedPubMedCentralCrossRefGoogle Scholar
  29. 29.
    Donnez O, Orellana R, Van Kerk O, Dehoux JP, Donnez J, Dolmans MM. Invasion process of induced deep nodular endometriosis in an experimental baboon model: similarities with collective cell migration? Fertil Steril. 2015;104(2):491–7. e2PubMedCrossRefGoogle Scholar
  30. 30.
    Patel B, Elguero S, Thakore S, Dahoud W, Bedaiwy M, Mesiano S. Role of nuclear progesterone receptor isoforms in uterine pathophysiology. Hum Reprod Update. 2015;21(2):155–73.PubMedCrossRefGoogle Scholar
  31. 31.
    Wetendorf M, DeMayo FJ. Progesterone receptor signaling in the initiation of pregnancy and preservation of a healthy uterus. Int J Dev Biol. 2014;58(2–4):95–106.PubMedPubMedCentralCrossRefGoogle Scholar
  32. 32.
    Ruiz-Alonso M, Blesa D, Simon C. The genomics of the human endometrium. Biochim Biophys Acta. 2012;1822(12):1931–42.PubMedCrossRefGoogle Scholar
  33. 33.
    Szwarc MM, Hai L, Gibbons WE, Peavey MC, White LD, Mo Q, et al. Human endometrial stromal cell decidualization requires transcriptional reprogramming by PLZF. Biol Reprod. 2018;98(1):15–27.PubMedCrossRefGoogle Scholar
  34. 34.
    Wang X, Wu SP, DeMayo FJ. Hormone dependent uterine epithelial-stromal communication for pregnancy support. Placenta. 2017;60(Suppl 1):S20–S6.PubMedPubMedCentralCrossRefGoogle Scholar
  35. 35.
    Li X, Large MJ, Creighton CJ, Lanz RB, Jeong JW, Young SL, et al. COUP-TFII regulates human endometrial stromal genes involved in inflammation. Mol Endocrinol. 2013;27(12):2041–54.PubMedPubMedCentralCrossRefGoogle Scholar
  36. 36.
    Jeong JW, Lee HS, Lee KY, White LD, Broaddus RR, Zhang YW, et al. Mig-6 modulates uterine steroid hormone responsiveness and exhibits altered expression in endometrial disease. Proc Natl Acad Sci U S A. 2009;106(21):8677–82.PubMedPubMedCentralCrossRefGoogle Scholar
  37. 37.
    Bhurke AS, Bagchi IC, Bagchi MK. Progesterone-regulated endometrial factors controlling implantation. Am J Reprod Immunol. 2016;75(3):237–45.PubMedPubMedCentralCrossRefGoogle Scholar
  38. 38.
    Hantak AM, Bagchi IC, Bagchi MK. Role of uterine stromal-epithelial crosstalk in embryo implantation. Int J Dev Biol. 2014;58(2–4):139–46.PubMedPubMedCentralCrossRefGoogle Scholar
  39. 39.
    Pawar S, Starosvetsky E, Orvis GD, Behringer RR, Bagchi IC, Bagchi MK. STAT3 regulates uterine epithelial remodeling and epithelial-stromal crosstalk during implantation. Mol Endocrinol. 2013;27(12):1996–2012.PubMedPubMedCentralCrossRefGoogle Scholar
  40. 40.
    Li Q, Kannan A, Das A, Demayo FJ, Hornsby PJ, Young SL, et al. WNT4 acts downstream of BMP2 and functions via beta-catenin signaling pathway to regulate human endometrial stromal cell differentiation. Endocrinology. 2013;154(1):446–57.PubMedCrossRefPubMedCentralGoogle Scholar
  41. 41.
    Wetendorf M, DeMayo FJ. The progesterone receptor regulates implantation, decidualization, and glandular development via a complex paracrine signaling network. Mol Cell Endocrinol. 2012;357(1–2):108–18.PubMedCrossRefPubMedCentralGoogle Scholar
  42. 42.
    Wu SP, Li R, DeMayo FJ. Progesterone receptor regulation of uterine adaptation for pregnancy. Trends Endocrinol Metab. 2018;29(7):481–91.PubMedPubMedCentralCrossRefGoogle Scholar
  43. 43.
    Afshar Y, Hastings J, Roqueiro D, Jeong JW, Giudice LC, Fazleabas AT. Changes in eutopic endometrial gene expression during the progression of experimental endometriosis in the baboon, Papio anubis. Biol Reprod. 2013;88(2):44.PubMedPubMedCentralCrossRefGoogle Scholar
  44. 44.
    Lessey BA, Young SL. Homeostasis imbalance in the endometrium of women with implantation defects: the role of estrogen and progesterone. Semin Reprod Med. 2014;32(5):365–75.PubMedCrossRefPubMedCentralGoogle Scholar
  45. 45.
    Young SL, Lessey BA. Progesterone function in human endometrium: clinical perspectives. Semin Reprod Med. 2010;28(1):5–16.PubMedCrossRefPubMedCentralGoogle Scholar
  46. 46.
    Joshi NR, Miyadahira EH, Afshar Y, Jeong JW, Young SL, Lessey BA, et al. Progesterone resistance in endometriosis is modulated by the altered expression of microRNA-29c and FKBP4. J Clin Endocrinol Metab. 2017;102(1):141–9.PubMedPubMedCentralGoogle Scholar
  47. 47.
    Barragan F, Irwin JC, Balayan S, Erikson DW, Chen JC, Houshdaran S, et al. Human endometrial fibroblasts derived from mesenchymal progenitors inherit progesterone resistance and acquire an inflammatory phenotype in the endometrial niche in endometriosis. Biol Reprod. 2016;94(5):118.PubMedPubMedCentralCrossRefGoogle Scholar
  48. 48.
    Burney RO, Talbi S, Hamilton AE, Vo KC, Nyegaard M, Nezhat CR, et al. Gene expression analysis of endometrium reveals progesterone resistance and candidate susceptibility genes in women with endometriosis. Endocrinology. 2007;148(8):3814–26.PubMedCrossRefGoogle Scholar
  49. 49.
    Evans J, Salamonsen LA, Winship A, Menkhorst E, Nie G, Gargett CE, et al. Fertile ground: human endometrial programming and lessons in health and disease. Nat Rev Endocrinol. 2016;12(11):654–67.PubMedCrossRefGoogle Scholar
  50. 50.
    Colon-Caraballo M, Garcia M, Mendoza A, Flores I. Human endometriosis tissue microarray reveals site-specific expression of estrogen receptors, progesterone receptor, and Ki67. Appl Immunohistochem Mol Morphol. 2018;27(7):491–500.CrossRefGoogle Scholar
  51. 51.
    Prentice A, Randall BJ, Weddell A, McGill A, Henry L, Horne CH, et al. Ovarian steroid receptor expression in endometriosis and in two potential parent epithelia: endometrium and peritoneal mesothelium. Hum Reprod. 1992;7(9):1318–25.PubMedCrossRefPubMedCentralGoogle Scholar
  52. 52.
    Igarashi TM, Bruner-Tran KL, Yeaman GR, Lessey BA, Edwards DP, Eisenberg E, et al. Reduced expression of progesterone receptor-B in the endometrium of women with endometriosis and in cocultures of endometrial cells exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin. Fertil Steril. 2005;84(1):67–74.PubMedCrossRefPubMedCentralGoogle Scholar
  53. 53.
    Bukulmez O, Hardy DB, Carr BR, Word RA, Mendelson CR. Inflammatory status influences aromatase and steroid receptor expression in endometriosis. Endocrinology. 2008;149(3):1190–204.PubMedCrossRefPubMedCentralGoogle Scholar
  54. 54.
    Gentilini D, Vigano P, Vignali M, Busacca M, Panina-Bordignon P, Caporizzo E, et al. Endometrial stromal progesterone receptor-A/progesterone receptor-B ratio: no difference between women with and without endometriosis. Fertil Steril. 2010;94(4):1538–40.PubMedCrossRefPubMedCentralGoogle Scholar
  55. 55.
    Bedaiwy MA, Dahoud W, Skomorovska-Prokvolit Y, Yi L, Liu JH, Falcone T, et al. Abundance and localization of progesterone receptor isoforms in endometrium in women with and without endometriosis and in peritoneal and ovarian endometriotic implants. Reprod Sci. 2015;22(9):1153–61.PubMedPubMedCentralCrossRefGoogle Scholar
  56. 56.
    Wolfler MM, Kuppers M, Rath W, Buck VU, Meinhold-Heerlein I, Classen-Linke I. Altered expression of progesterone receptor isoforms A and B in human eutopic endometrium in endometriosis patients. Ann Anat. 2016;206:1–6.PubMedCrossRefPubMedCentralGoogle Scholar
  57. 57.
    McKinnon B, Mueller M, Montgomery G. Progesterone resistance in endometriosis: an acquired property? Trends Endocrinol Metab. 2018;29(8):535–48.PubMedCrossRefPubMedCentralGoogle Scholar
  58. 58.
    Al-Sabbagh M, Lam EW, Brosens JJ. Mechanisms of endometrial progesterone resistance. Mol Cell Endocrinol. 2012;358(2):208–15.PubMedCrossRefPubMedCentralGoogle Scholar
  59. 59.
    Aghajanova L, Tatsumi K, Horcajadas JA, Zamah AM, Esteban FJ, Herndon CN, et al. Unique transcriptome, pathways, and networks in the human endometrial fibroblast response to progesterone in endometriosis. Biol Reprod. 2011;84(4):801–15.PubMedCrossRefPubMedCentralGoogle Scholar
  60. 60.
    Zhao L, Gu C, Ye M, Zhang Z, Li L, Fan W, et al. Integration analysis of microRNA and mRNA paired expression profiling identifies deregulated microRNA-transcription factor-gene regulatory networks in ovarian endometriosis. Reprod Biol Endocrinol. 2018;16(1):4.PubMedPubMedCentralCrossRefGoogle Scholar
  61. 61.
    Yotova I, Hsu E, Do C, Gaba A, Sczabolcs M, Dekan S, et al. Epigenetic alterations affecting transcription factors and signaling pathways in stromal cells of endometriosis. PLoS One. 2017;12(1):e0170859.PubMedPubMedCentralCrossRefGoogle Scholar
  62. 62.
    Warren LA, Shih A, Renteira SM, Seckin T, Blau B, Simpfendorfer K, et al. Analysis of menstrual effluent: diagnostic potential for endometriosis. Mol Med. 2018;24(1):1.PubMedPubMedCentralCrossRefGoogle Scholar
  63. 63.
    Houshdaran S, Nezhat CR, Vo KC, Zelenko Z, Irwin JC, Giudice LC. Aberrant endometrial DNA methylome and associated gene expression in women with endometriosis. Biol Reprod. 2016;95(5):93.PubMedPubMedCentralCrossRefGoogle Scholar
  64. 64.
    Bulun SE, Monsivais D, Kakinuma T, Furukawa Y, Bernardi L, Pavone ME, et al. Molecular biology of endometriosis: from aromatase to genomic abnormalities. Semin Reprod Med. 2015;33(3):220–4.PubMedCrossRefPubMedCentralGoogle Scholar
  65. 65.
    Hawkins SM, Creighton CJ, Han DY, Zariff A, Anderson ML, Gunaratne PH, et al. Functional microRNA involved in endometriosis. Mol Endocrinol. 2011;25(5):821–32.PubMedPubMedCentralCrossRefGoogle Scholar
  66. 66.
    Fazleabas AT. Progesterone resistance in a baboon model of endometriosis. Semin Reprod Med. 2010;28(1):75–80.PubMedCrossRefPubMedCentralGoogle Scholar
  67. 67.
    Yoo JY, Jeong JW, Fazleabas AT, Tayade C, Young SL, Lessey BA. Protein inhibitor of activated STAT3 (PIAS3) is Down-regulated in eutopic endometrium of women with endometriosis. Biol Reprod. 2016;95(1):11.PubMedPubMedCentralCrossRefGoogle Scholar
  68. 68.
    Yoo JY, Kim TH, Fazleabas AT, Palomino WA, Ahn SH, Tayade C, et al. KRAS activation and over-expression of SIRT1/BCL6 contributes to the pathogenesis of endometriosis and progesterone resistance. Sci Rep. 2017;7(1):6765.PubMedPubMedCentralCrossRefGoogle Scholar
  69. 69.
    Ahn JI, Yoo JY, Kim TH, Kim YI, Ferguson SD, Fazleabas AT, et al. cAMP-response element-binding 3-like protein 1 (CREB3L1) is required for decidualization and its expression is decreased in women with endometriosis. Curr Mol Med. 2016;16(3):276–87.PubMedPubMedCentralCrossRefGoogle Scholar
  70. 70.
    Yoo JY, Shin H, Kim TH, Choi WS, Ferguson SD, Fazleabas AT, et al. CRISPLD2 is a target of progesterone receptor and its expression is decreased in women with endometriosis. PLoS One. 2014;9(6):e100481.PubMedPubMedCentralCrossRefGoogle Scholar
  71. 71.
    Kurihara I, Lee DK, Petit FG, Jeong J, Lee K, Lydon JP, et al. COUP-TFII mediates progesterone regulation of uterine implantation by controlling ER activity. PLoS Genet. 2007;3(6):e102.PubMedPubMedCentralCrossRefGoogle Scholar
  72. 72.
    Lee DK, Kurihara I, Jeong JW, Lydon JP, DeMayo FJ, Tsai MJ, et al. Suppression of ERalpha activity by COUP-TFII is essential for successful implantation and decidualization. Mol Endocrinol. 2010;24(5):930–40.PubMedPubMedCentralCrossRefGoogle Scholar
  73. 73.
    Bulun SE, Cheng YH, Yin P, Imir G, Utsunomiya H, Attar E, et al. Progesterone resistance in endometriosis: link to failure to metabolize estradiol. Mol Cell Endocrinol. 2006;248(1–2):94–103.PubMedCrossRefPubMedCentralGoogle Scholar
  74. 74.
    Aghajanova L, Velarde MC, Giudice LC. Altered gene expression profiling in endometrium: evidence for progesterone resistance. Semin Reprod Med. 2010;28(1):51–8.PubMedCrossRefPubMedCentralGoogle Scholar
  75. 75.
    Benson G, Lim H, Paria B, Satokata I, Dey S, Maas R, et al. Mechanisms of reduced fertility in Hoxa-10 mutant mice: uterine homeosis and loss of maternal Hoxa-10 expression. Development. 1996;122:2687–96.PubMedPubMedCentralGoogle Scholar
  76. 76.
    Taylor HS, Arici A, Olive D, Igarashi P. HOXA10 is expressed in response to sex steroids at the time of implantation in the human endometrium. J Clin Invest. 1998;101(7):1379–84.PubMedPubMedCentralCrossRefGoogle Scholar
  77. 77.
    Daftary GS, Taylor HS. Endocrine regulation of HOX genes. Endocr Rev. 2006;27(4):331–55.PubMedCrossRefPubMedCentralGoogle Scholar
  78. 78.
    Kim JJ, Taylor HS, Lu Z, Ladhani O, Hastings JM, Jackson KS, et al. Altered expression of HOXA10 in endometriosis: potential role in decidualization. Mol Hum Reprod. 2007;13(5):323–32.PubMedCrossRefPubMedCentralGoogle Scholar
  79. 79.
    Godbole GB, Modi DN, Puri CP. Regulation of homeobox A10 expression in the primate endometrium by progesterone and embryonic stimuli. Reproduction. 2007;134(3):513–23.PubMedCrossRefPubMedCentralGoogle Scholar
  80. 80.
    Lu Z, Hardt J, Kim JJ. Global analysis of genes regulated by HOXA10 in decidualization reveals a role in cell proliferation. Mol Hum Reprod. 2008;14(6):357–66.PubMedPubMedCentralCrossRefGoogle Scholar
  81. 81.
    Gellersen B, Brosens IA, Brosens JJ. Decidualization of the human endometrium: mechanisms, functions, and clinical perspectives. Semin Reprod Med. 2007;25(6):445–53.CrossRefGoogle Scholar
  82. 82.
    Kim JJ, Buzzio OL, Li S, Lu Z. Role of FOXO1A in the regulation of insulin-like growth factor-binding protein-1 in human endometrial cells: interaction with progesterone receptor. Biol Reprod. 2005;73(4):833–9.PubMedPubMedCentralCrossRefGoogle Scholar
  83. 83.
    Kim JJ, Taylor H, Akbas G, Foucher I, Trembleau A, Jaffe R, et al. Regulation of insulin-like growth factor binding protein-1 promoter activity by FKHR and HOXA10 in primate endometrial cells. Biol Reprod. 2003;68(1):24–30.PubMedCrossRefGoogle Scholar
  84. 84.
    Celik O, Unlu C, Otlu B, Celik N, Caliskan E. Laparoscopic endometrioma resection increases peri-implantation endometrial HOXA-10 and HOXA-11 mRNA expression. Fertil Steril. 2015;104(2):356–65.PubMedCrossRefGoogle Scholar
  85. 85.
    Wu Y, Halverson G, Basir Z, Strawn E, Yan P, Guo SW. Aberrant methylation at HOXA10 may be responsible for its aberrant expression in the endometrium of patients with endometriosis. Am J Obstet Gynecol. 2005;193(2):371–80.PubMedCrossRefGoogle Scholar
  86. 86.
    Szczepanska M, Wirstlein P, Luczak M, Jagodzinski PP, Skrzypczak J. Reduced expression of HOXA10 in the midluteal endometrium from infertile women with minimal endometriosis. Biomed Pharmacother. 2010;64(10):697–705.PubMedCrossRefGoogle Scholar
  87. 87.
    Andersson KL, Bussani C, Fambrini M, Polverino V, Taddei GL, Gemzell-Danielsson K, et al. DNA methylation of HOXA10 in eutopic and ectopic endometrium. Hum Reprod. 2014;29(9):1906–11.PubMedCrossRefGoogle Scholar
  88. 88.
    Ji F, Yang X, He Y, Wang H, Aili A, Ding Y. Aberrant endometrial DNA methylome of homeobox A10 and catechol-O-methyltransferase in endometriosis. J Assist Reprod Genet. 2017;34(3):409–15.PubMedPubMedCentralCrossRefGoogle Scholar
  89. 89.
    Lu H, Yang X, Zhang Y, Lu R, Wang X. Epigenetic disorder may cause downregulation of HOXA10 in the eutopic endometrium of fertile women with endometriosis. Reprod Sci. 2013;20(1):78–84.PubMedCrossRefGoogle Scholar
  90. 90.
    Samadieh Y, Favaedi R, Ramezanali F, Afsharian P, Aflatoonian R, Shahhoseini M. Epigenetic dynamics of HOXA10 gene in infertile women with endometriosis. Reprod Sci. 2018;  https://doi.org/10.1177/1933719118766255.PubMedCrossRefGoogle Scholar
  91. 91.
    Petracco R, Grechukhina O, Popkhadze S, Massasa E, Zhou Y, Taylor HS. MicroRNA 135 regulates HOXA10 expression in endometriosis. J Clin Endocrinol Metab. 2011;96(12):E1925–33.PubMedPubMedCentralCrossRefGoogle Scholar
  92. 92.
    Mirabutalebi SH, Karami N, Montazeri F, Fesahat F, Sheikhha MH, Hajimaqsoodi E, et al. The relationship between the expression levels of miR-135a and HOXA10 gene in the eutopic and ectopic endometrium. Int J Reprod Biomed. 2018;16(8):501–6.CrossRefGoogle Scholar
  93. 93.
    Du T, Zamore PD. microPrimer: the biogenesis and function of microRNA. Development. 2005;132(21):4645–52.PubMedCrossRefGoogle Scholar
  94. 94.
    Zhu XM, Han T, Sargent IL, Yin GW, Yao YQ. Differential expression profile of microRNAs in human placentas from preeclamptic pregnancies vs normal pregnancies. Am J Obstet Gynecol. 2009;200(6):661.e1–7.CrossRefGoogle Scholar
  95. 95.
    Chung TK, Cheung TH, Huen NY, Wong KW, Lo KW, Yim SF, et al. Dysregulated microRNAs and their predicted targets associated with endometrioid endometrial adenocarcinoma in Hong Kong women. Int J Cancer. 2009;124(6):1358–65.CrossRefGoogle Scholar
  96. 96.
    Wang T, Zhang X, Obijuru L, Laser J, Aris V, Lee P, et al. A micro-RNA signature associated with race, tumor size, and target gene activity in human uterine leiomyomas. Genes Chromosomes Cancer. 2007;46(4):336–47.CrossRefGoogle Scholar
  97. 97.
    Marsh EE, Lin Z, Yin P, Milad M, Chakravarti D, Bulun SE. Differential expression of microRNA species in human uterine leiomyoma versus normal myometrium. Fertil Steril. 2008;89(6):1771–6.CrossRefGoogle Scholar
  98. 98.
    Nagaraja AK, Creighton CJ, Yu Z, Zhu H, Gunaratne PH, Reid JG, et al. A link between mir-100 and FRAP1/mTOR in clear cell ovarian cancer. Mol Endocrinol. 2010;24(2):447–63.PubMedPubMedCentralCrossRefGoogle Scholar
  99. 99.
    Creighton CJ, Benham AL, Zhu H, Khan MF, Reid JG, Nagaraja AK, et al. Discovery of novel microRNAs in female reproductive tract using next generation sequencing. PLoS One. 2010;5(3):e9637.PubMedPubMedCentralCrossRefGoogle Scholar
  100. 100.
    Zhang L, Volinia S, Bonome T, Calin GA, Greshock J, Yang N, et al. Genomic and epigenetic alterations deregulate microRNA expression in human epithelial ovarian cancer. Proc Natl Acad Sci U S A. 2008;105(19):7004–9.PubMedPubMedCentralCrossRefGoogle Scholar
  101. 101.
    Ohlsson Teague EM, Van der Hoek KH, Van der Hoek MB, Perry N, Wagaarachchi P, Robertson SA, et al. MicroRNA-regulated pathways associated with endometriosis. Mol Endocrinol. 2009;23(2):265–75.PubMedPubMedCentralCrossRefGoogle Scholar
  102. 102.
    Burney RO, Hamilton AE, Aghajanova L, Vo KC, Nezhat CN, Lessey BA, et al. MicroRNA expression profiling of eutopic secretory endometrium in women with versus without endometriosis. Mol Hum Reprod. 2009;15(10):625–31.PubMedPubMedCentralCrossRefGoogle Scholar
  103. 103.
    Teague EM, Print CG, Hull ML. The role of microRNAs in endometriosis and associated reproductive conditions. Hum Reprod Update. 2010;16(2):142–65.PubMedCrossRefPubMedCentralGoogle Scholar
  104. 104.
    Haikalis ME, Wessels JM, Leyland NA, Agarwal SK, Foster WG. MicroRNA expression pattern differs depending on endometriosis lesion type. Biol Reprod. 2018;98(5):623–33.PubMedCrossRefPubMedCentralGoogle Scholar
  105. 105.
    Rekker K, Tasa T, Saare M, Samuel K, Kadastik U, Karro H, et al. Differentially-expressed miRNAs in ectopic stromal cells contribute to endometriosis development: the plausible role of miR-139-5p and miR-375. Int J Mol Sci. 2018;19(12):E3789.PubMedCrossRefPubMedCentralGoogle Scholar
  106. 106.
    Joshi NR, Su RW, Chandramouli GV, Khoo SK, Jeong JW, Young SL, et al. Altered expression of microRNA-451 in eutopic endometrium of baboons (Papio anubis) with endometriosis. Hum Reprod. 2015;30(12):2881–91.PubMedPubMedCentralGoogle Scholar
  107. 107.
    Aghajanova L, Giudice LC. Molecular evidence for differences in endometrium in severe versus mild endometriosis. Reprod Sci. 2011;18(3):229–51.PubMedPubMedCentralCrossRefGoogle Scholar
  108. 108.
    Filigheddu N, Gregnanin I, Porporato PE, Surico D, Perego B, Galli L, et al. Differential expression of microRNAs between eutopic and ectopic endometrium in ovarian endometriosis. J Biomed Biotechnol. 2010;2010:369549.PubMedPubMedCentralCrossRefGoogle Scholar
  109. 109.
    Hull ML, Nisenblat V. Tissue and circulating microRNA influence reproductive function in endometrial disease. Reprod Biomed Online. 2013;27(5):515–29.PubMedCrossRefPubMedCentralGoogle Scholar
  110. 110.
    Nothnick WB. MicroRNAs and endometriosis: distinguishing drivers from passengers in disease pathogenesis. Semin Reprod Med. 2017;35(2):173–80.PubMedPubMedCentralCrossRefGoogle Scholar
  111. 111.
    Gilabert-Estelles J, Braza-Boils A, Ramon LA, Zorio E, Medina P, Espana F, et al. Role of microRNAs in gynecological pathology. Curr Med Chem. 2012;19(15):2406–13.PubMedCrossRefPubMedCentralGoogle Scholar
  112. 112.
    Pei T, Liu C, Liu T, Xiao L, Luo B, Tan J, et al. miR-194-3p represses the progesterone receptor and decidualization in eutopic endometrium from women with wndometriosis. Endocrinology. 2018;159(7):2554–62.PubMedCrossRefPubMedCentralGoogle Scholar
  113. 113.
    Zhou M, Fu J, Xiao L, Yang S, Song Y, Zhang X, et al. miR-196a overexpression activates the MEK/ERK signal and represses the progesterone receptor and decidualization in eutopic endometrium from women with endometriosis. Hum Reprod. 2016;31(11):2598–608.PubMedCrossRefPubMedCentralGoogle Scholar
  114. 114.
    Sultana S, Kajihara T, Mizuno Y, Sato T, Oguro T, Kimura M, et al. Overexpression of microRNA-542-3p attenuates the differentiating capacity of endometriotic stromal cells. Reprod Med Biol. 2017;16(2):170–8.PubMedPubMedCentralCrossRefGoogle Scholar
  115. 115.
    Yang P, Wu Z, Ma C, Pan N, Wang Y, Yan L. Endometrial miR-543 is downregulated during the implantation window in women with endometriosis-related infertility. Reprod Sci. 2018;26(7):900–8.  https://doi.org/10.1177/1933719118799199.CrossRefPubMedPubMedCentralGoogle Scholar
  116. 116.
    Agarwal V, Bell GW, Nam JW, Bartel DP. Predicting effective microRNA target sites in mammalian mRNAs. Elife. 2015;4  https://doi.org/10.7554/eLife.05005.
  117. 117.
    Friedman RC, Farh KK, Burge CB, Bartel DP. Most mammalian mRNAs are conserved targets of microRNAs. Genome Res. 2009;19(1):92–105.PubMedPubMedCentralCrossRefGoogle Scholar
  118. 118.
    Tranguch S, Wang H, Daikoku T, Xie H, Smith DF, Dey SK. FKBP52 deficiency-conferred uterine progesterone resistance is genetic background and pregnancy stage specific. J Clin Invest. 2007;117(7):1824–34.PubMedPubMedCentralCrossRefGoogle Scholar
  119. 119.
    Jackson KS, Brudney A, Hastings JM, Mavrogianis PA, Kim JJ, Fazleabas AT. The altered distribution of the steroid hormone receptors and the chaperone immunophilin FKBP52 in a baboon model of endometriosis is associated with progesterone resistance during the window of uterine receptivity. Reprod Sci. 2007;14(2):137–50.PubMedCrossRefPubMedCentralGoogle Scholar
  120. 120.
    Yang H, Zhou Y, Edelshain B, Schatz F, Lockwood CJ, Taylor HS. FKBP4 is regulated by HOXA10 during decidualization and in endometriosis. Reproduction. 2012;143(4):531–8.PubMedCrossRefGoogle Scholar
  121. 121.
    Aghajanova L, Hamilton A, Kwintkiewicz J, Vo KC, Giudice LC. Steroidogenic enzyme and key decidualization marker dysregulation in endometrial stromal cells from women with versus without endometriosis. Biol Reprod. 2009;80(1):105–14.PubMedPubMedCentralCrossRefGoogle Scholar
  122. 122.
    Klemmt PA, Carver JG, Kennedy SH, Koninckx PR, Mardon HJ. Stromal cells from endometriotic lesions and endometrium from women with endometriosis have reduced decidualization capacity. Fertil Steril. 2006;85(3):564–72.PubMedPubMedCentralCrossRefGoogle Scholar
  123. 123.
    Koike N, Higashiura Y, Akasaka J, Uekuri C, Ito F, Kobayashi H. Epigenetic dysregulation of endometriosis susceptibility genes (Review). Mol Med Rep. 2015;12(2):1611–6.PubMedCrossRefGoogle Scholar
  124. 124.
    Xue Q, Lin Z, Cheng YH, Huang CC, Marsh E, Yin P, et al. Promoter methylation regulates estrogen receptor 2 in human endometrium and endometriosis. Biol Reprod. 2007;77(4):681–7.PubMedCrossRefGoogle Scholar
  125. 125.
    Wu Y, Strawn E, Basir Z, Halverson G, Guo SW. Promoter hypermethylation of progesterone receptor isoform B (PR-B) in endometriosis. Epigenetics. 2006;1(2):106–11.PubMedCrossRefGoogle Scholar
  126. 126.
    Dyson MT, Roqueiro D, Monsivais D, Ercan CM, Pavone ME, Brooks DC, et al. Genome-wide DNA methylation analysis predicts an epigenetic switch for GATA factor expression in endometriosis. PLoS Genet. 2014;10(3):e1004158.PubMedPubMedCentralCrossRefGoogle Scholar
  127. 127.
    Kulp JL, Mamillapalli R, Taylor HS. Aberrant HOXA10 methylation in patients with common gynecologic disorders: implications for reproductive outcomes. Reprod Sci. 2016;23(4):455–63.PubMedPubMedCentralCrossRefGoogle Scholar
  128. 128.
    Brooks GD, McLeod L, Alhayyani S, Miller A, Russell PA, Ferlin W, et al. IL6 trans-signaling promotes KRAS-driven lung carcinogenesis. Cancer Res. 2016;76(4):866–76.PubMedCrossRefGoogle Scholar
  129. 129.
    Cheng CW, Licence D, Cook E, Luo F, Arends MJ, Smith SK, et al. Activation of mutated K-ras in donor endometrial epithelium and stroma promotes lesion growth in an intact immunocompetent murine model of endometriosis. J Pathol. 2011;224(2):261–9.PubMedCrossRefGoogle Scholar
  130. 130.
    Grandi G, Mueller MD, Papadia A, Kocbek V, Bersinger NA, Petraglia F, et al. Inflammation influences steroid hormone receptors targeted by progestins in endometrial stromal cells from women with endometriosis. J Reprod Immunol. 2016;117:30–8.PubMedCrossRefGoogle Scholar
  131. 131.
    Bulun SE, Monsavais D, Pavone ME, Dyson M, Xue Q, Attar E, et al. Role of estrogen receptor-beta in endometriosis. Semin Reprod Med. 2012;30(1):39–45.PubMedPubMedCentralCrossRefGoogle Scholar
  132. 132.
    Smuc T, Hevir N, Ribic-Pucelj M, Husen B, Thole H, Rizner TL. Disturbed estrogen and progesterone action in ovarian endometriosis. Mol Cell Endocrinol. 2009;301(1–2):59–64.PubMedCrossRefGoogle Scholar
  133. 133.
    Han SJ, Jung SY, Wu SP, Hawkins SM, Park MJ, Kyo S, et al. Estrogen receptor beta modulates apoptosis complexes and the inflammasome to drive the pathogenesis of endometriosis. Cell. 2015;163(4):960–74.PubMedPubMedCentralCrossRefGoogle Scholar
  134. 134.
    Bulun SE, Zeitoun KM, Takayama K, Sasano H. Estrogen biosynthesis in endometriosis: molecular basis and clinical relevance. J Mol Endocrinol. 2000;25(1):35–42.PubMedCrossRefPubMedCentralGoogle Scholar
  135. 135.
    Langoi D, Pavone ME, Gurates B, Chai D, Fazleabas A, Bulun SE. Aromatase inhibitor treatment limits progression of peritoneal endometriosis in baboons. Fertil Steril. 2013;99(3):656–62.e3.PubMedCrossRefPubMedCentralGoogle Scholar
  136. 136.
    Li Q, Kannan A, DeMayo FJ, Lydon JP, Cooke PS, Yamagishi H, et al. The antiproliferative action of progesterone in uterine epithelium is mediated by Hand2. Science. 2011;331(6019):912–6.PubMedPubMedCentralCrossRefGoogle Scholar
  137. 137.
    Lee K, Jeong J, Kwak I, Yu CT, Lanske B, Soegiarto DW, et al. Indian hedgehog is a major mediator of progesterone signaling in the mouse uterus. Nat Genet. 2006;38(10):1204–9.PubMedCrossRefPubMedCentralGoogle Scholar
  138. 138.
    Lessey BA, Kim JJ. Endometrial receptivity in the eutopic endometrium of women with endometriosis: it is affected, and let me show you why. Fertil Steril. 2017;108(1):19–27.PubMedPubMedCentralCrossRefGoogle Scholar
  139. 139.
    Marcoux S, Maheux R, Berube S. Laparoscopic surgery in infertile women with minimal or mild endometriosis. Canadian Collaborative Group on Endometriosis. N Engl J Med. 1997;337(4):217–22.PubMedCrossRefGoogle Scholar
  140. 140.
    Jacobson TZ, Barlow DH, Koninckx PR, Olive D, Farquhar C. Laparoscopic surgery for subfertility associated with endometriosis. Cochrane Database Syst Rev. 2002;(4):CD001398.Google Scholar
  141. 141.
    Simon C, Gutierrez A, Vidal A. de los Santos MJ, Tarin JJ, Remohi J, et al. Outcome of patients with endometriosis in assisted reproduction: results from in-vitro fertilization and oocyte donation. Hum Reprod. 1994;9(4):725–9.CrossRefGoogle Scholar
  142. 142.
    Prapas Y, Goudakou M, Matalliotakis I, Kalogeraki A, Matalliotaki C, Panagiotidis Y, et al. History of endometriosis may adversely affect the outcome in menopausal recipients of sibling oocytes. Reprod Biomed Online. 2012;25(5):543–8.CrossRefGoogle Scholar
  143. 143.
    Braundmeier A, Jackson K, Hastings J, Koehler J, Nowak R, Fazleabas A. Induction of endometriosis alters the peripheral and endometrial regulatory T cell population in the non-human primate. Hum Reprod. 2012;27(6):1712–22.PubMedPubMedCentralCrossRefGoogle Scholar
  144. 144.
    Maruyama T, Yoshimura Y. Molecular and cellular mechanisms for differentiation and regeneration of the uterine endometrium. Endocr J. 2008;55(5):795–810.PubMedCrossRefPubMedCentralGoogle Scholar
  145. 145.
    Minici F, Tiberi F, Tropea A, Orlando M, Gangale MF, Romani F, et al. Endometriosis and human infertility: a new investigation into the role of eutopic endometrium. Hum Reprod. 2008;23(3):530–7.PubMedCrossRefPubMedCentralGoogle Scholar
  146. 146.
    Su RW, Strug MR, Joshi NR, Jeong JW, Miele L, Lessey BA, et al. Decreased Notch pathway signaling in the endometrium of women with endometriosis impairs decidualization. J Clin Endocrinol Metab. 2015;100(3):E433–42.PubMedCrossRefPubMedCentralGoogle Scholar
  147. 147.
    Afshar Y, Miele L, Fazleabas AT. Notch1 is regulated by chorionic gonadotropin and progesterone in endometrial stromal cells and modulates decidualization in primates. Endocrinology. 2012;153(6):2884–96.PubMedPubMedCentralCrossRefGoogle Scholar
  148. 148.
    Afshar Y, Jeong JW, Roqueiro D, DeMayo F, Lydon J, Radtke F, et al. Notch1 mediates uterine stromal differentiation and is critical for complete decidualization in the mouse. FASEB J. 2012;26(1):282–94.PubMedPubMedCentralCrossRefGoogle Scholar
  149. 149.
    Takano M, Lu Z, Goto T, Fusi L, Higham J, Francis J, et al. Transcriptional cross talk between the forkhead transcription factor forkhead box O1A and the progesterone receptor coordinates cell cycle regulation and differentiation in human endometrial stromal cells. Mol Endocrinol. 2007;21(10):2334–49.PubMedCrossRefPubMedCentralGoogle Scholar
  150. 150.
    Vasquez YM, Mazur EC, Li X, Kommagani R, Jiang L, Chen R, et al. FOXO1 is required for binding of PR on IRF4, novel transcriptional regulator of endometrial stromal decidualization. Mol Endocrinol. 2015;29(3):421–33.PubMedPubMedCentralCrossRefGoogle Scholar
  151. 151.
    Kim JJ, Fazleabas AT. Uterine receptivity and implantation: the regulation and action of insulin-like growth factor binding protein-1 (IGFBP-1), HOXA10 and forkhead transcription factor-1 (FOXO-1) in the baboon endometrium. Reprod Biol Endocrinol. 2004;2:34.PubMedPubMedCentralCrossRefGoogle Scholar
  152. 152.
    Brown DM, Lee HC, Liu S, Quick CM, Fernandes LM, Simmen FA, et al. Notch-1 signaling activation and progesterone receptor expression in ectopic lesions of women with endometriosis. J Endocr Soc. 2018;2(7):765–78.PubMedPubMedCentralCrossRefGoogle Scholar
  153. 153.
    Yin X, Pavone ME, Lu Z, Wei J, Kim JJ. Increased activation of the PI3K/AKT pathway compromises decidualization of stromal cells from endometriosis. J Clin Endocrinol Metab. 2012;97(1):E35–43.PubMedCrossRefGoogle Scholar
  154. 154.
    Yoshino O, Osuga Y, Hirota Y, Koga K, Yano T, Tsutsumi O, et al. Akt as a possible intracellular mediator for decidualization in human endometrial stromal cells. Mol Hum Reprod. 2003;9(5):265–9.PubMedCrossRefGoogle Scholar
  155. 155.
    Campbell RA, Bhat-Nakshatri P, Patel NM, Constantinidou D, Ali S, Nakshatri H. Phosphatidylinositol 3-kinase/AKT-mediated activation of estrogen receptor alpha: a new model for anti-estrogen resistance. J Biol Chem. 2001;276(13):9817–24.PubMedCrossRefGoogle Scholar
  156. 156.
    Sanchez M, Sauve K, Picard N, Tremblay A. The hormonal response of estrogen receptor beta is decreased by the phosphatidylinositol 3-kinase/Akt pathway via a phosphorylation-dependent release of CREB-binding protein. J Biol Chem. 2007;282(7):4830–40.PubMedCrossRefGoogle Scholar
  157. 157.
    Eaton JL, Unno K, Caraveo M, Lu Z, Kim JJ. Increased AKT or MEK1/2 activity influences progesterone receptor levels and localization in endometriosis. J Clin Endocrinol Metab. 2013;98(12):E1871–9.PubMedPubMedCentralCrossRefGoogle Scholar
  158. 158.
    McKinnon BD, Kocbek V, Nirgianakis K, Bersinger NA, Mueller MD. Kinase signalling pathways in endometriosis: potential targets for non-hormonal therapeutics. Hum Reprod Update. 2016;22(3):382–403.PubMedCrossRefGoogle Scholar
  159. 159.
    Uimari O, Rahmioglu N, Nyholt DR, Vincent K, Missmer SA, Becker C, et al. Genome-wide genetic analyses highlight mitogen-activated protein kinase (MAPK) signaling in the pathogenesis of endometriosis. Hum Reprod. 2017;32(4):780–93.PubMedPubMedCentralCrossRefGoogle Scholar
  160. 160.
    Mormile R, Vittori G. MAPK signaling pathway and endometriosis: what is the link? Arch Gynecol Obstet. 2013;287(4):837–8.PubMedCrossRefPubMedCentralGoogle Scholar
  161. 161.
    Zhou WD, Chen QH, Chen QX. The action of p38 MAP kinase and its inhibitors on endometriosis. Yao Xue Xue Bao. 2010;45(5):548–54.PubMedGoogle Scholar
  162. 162.
    Yoshino O, Osuga Y, Hirota Y, Koga K, Hirata T, Harada M, et al. Possible pathophysiological roles of mitogen-activated protein kinases (MAPKs) in endometriosis. Am J Reprod Immunol. 2004;52(5):306–11.PubMedCrossRefPubMedCentralGoogle Scholar
  163. 163.
    Kim EK, Choi EJ. Pathological roles of MAPK signaling pathways in human diseases. Biochim Biophys Acta. 2010;1802(4):396–405.PubMedCrossRefPubMedCentralGoogle Scholar
  164. 164.
    Matsuzaki S, Darcha C. Co-operation between the AKT and ERK signaling pathways may support growth of deep endometriosis in a fibrotic microenvironment in vitro. Hum Reprod. 2015;30(7):1606–16.PubMedCrossRefPubMedCentralGoogle Scholar
  165. 165.
    Yotova IY, Quan P, Leditznig N, Beer U, Wenzl R, Tschugguel W. Abnormal activation of Ras/Raf/MAPK and RhoA/ROCKII signalling pathways in eutopic endometrial stromal cells of patients with endometriosis. Hum Reprod. 2011;26(4):885–97.PubMedCrossRefPubMedCentralGoogle Scholar
  166. 166.
    Ngo C, Nicco C, Leconte M, Chereau C, Arkwright S, Vacher-Lavenu MC, et al. Protein kinase inhibitors can control the progression of endometriosis in vitro and in vivo. J Pathol. 2010;222(2):148–57.PubMedCrossRefPubMedCentralGoogle Scholar
  167. 167.
    Leconte M, Nicco C, Ngo C, Arkwright S, Chereau C, Guibourdenche J, et al. Antiproliferative effects of cannabinoid agonists on deep infiltrating endometriosis. Am J Pathol. 2010;177(6):2963–70.PubMedPubMedCentralCrossRefGoogle Scholar
  168. 168.
    Wu Y, Kajdacsy-Balla A, Strawn E, Basir Z, Halverson G, Jailwala P, et al. Transcriptional characterizations of differences between eutopic and ectopic endometrium. Endocrinology. 2006;147(1):232–46.PubMedCrossRefPubMedCentralGoogle Scholar
  169. 169.
    Velarde MC, Aghajanova L, Nezhat CR, Giudice LC. Increased mitogen-activated protein kinase kinase/extracellularly regulated kinase activity in human endometrial stromal fibroblasts of women with endometriosis reduces 3′,5′-cyclic adenosine 5′-monophosphate inhibition of cyclin D1. Endocrinology. 2009;150(10):4701–12.PubMedPubMedCentralCrossRefGoogle Scholar
  170. 170.
    Lee CH, Kim TH, Lee JH, Oh SJ, Yoo JY, Kwon HS, et al. Extracellular signal-regulated kinase 1/2 signaling pathway is required for endometrial decidualization in mice and human. PLoS One. 2013;8(9):e75282.PubMedPubMedCentralCrossRefGoogle Scholar
  171. 171.
    Wu MH, Lin SC, Hsiao KY, Tsai SJ. Hypoxia-inhibited dual-specificity phosphatase-2 expression in endometriotic cells regulates cyclooxygenase-2 expression. J Pathol. 2011;225(3):390–400.PubMedCrossRefGoogle Scholar
  172. 172.
    Lin SC, Wang CC, Wu MH, Yang SH, Li YH, Tsai SJ. Hypoxia-induced microRNA-20a expression increases ERK phosphorylation and angiogenic gene expression in endometriotic stromal cells. J Clin Endocrinol Metab. 2012;97(8):E1515–23.CrossRefGoogle Scholar
  173. 173.
    Kim BG, Yoo J-Y, Kim TH, Shin J-H, Langenheim JF, Ferguson SD, et al. Aberrant activation of signal transducer and activator of transcription-3 (STAT3) signaling in endometriosis. Hum Reprod. 2015;30(5):1069–78.PubMedPubMedCentralCrossRefGoogle Scholar
  174. 174.
    Yoo J-Y, Jeong J-W, Fazleabas AT, Tayade C, Young SL, Lessey BA. Protein inhibitor of activated STAT3 (PIAS3) is Down-regulated in eutopic endometrium of women with endometriosis1. Biol Reprod. 2016;95(1):11, 1–7–, 1–7.PubMedPubMedCentralCrossRefGoogle Scholar
  175. 175.
    Walker SR, Nelson EA, Yeh JE, Pinello L, Yuan G-C, Frank DA. STAT5 outcompetes STAT3 to regulate the expression of the oncogenic transcriptional modulator BCL6. Mol Cell Biol. 2013;33(15):2879–90.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  1. 1.Department of Obstetrics, Gynecology and Reproductive BiologyCollege of Human Medicine, Michigan State UniversityGrand RapidsUSA
  2. 2.College of Veterinary Medicine, South China Agricultural UniversityGuangzhou, GuangdongChina

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