Apoptosis in Endometriosis

Endometriosis is an inflammatory, estrogen-dependent disease characterized by the growth of endometrial tissues outside the uterus. The eutopic endometrium from women with endometriosis has some fundamental differences compared with the normal endometrium of women without endometriosis. The differences could contribute to the survival of regurgitating endometrial cells into the peritoneal cavity and the development of endometriosis. One mechanism that gained a lot of interests is the finding that apoptosis appeared in eutopic and ectopic endometrium of patients with endometriosis. A common characteristic of endometriotic cells is their ability to evade the apoptotic machinery. Endometriosis could result from increased cellular proliferation or decreased apoptosis in response to appropriate stimuli. This chapter focused on the physiological role of apoptosis in normal endometrium and the alterations in regulation of apoptosis in eutopic and ectopic endometrium from women with endometriosis. Finally, the role of apoptosis in the treatment of endometriosis is reviewed to link the basic research findings into clinical applications. Access this chapter Tax calculation will be finalised at checkout Purchases are for personal use only Similar content being viewed by others

Halme J, Hammond MG, Hulka JF, Raj S, Talbert LM. Retrograde menstruation in healthy women and in patients with endometriosis. Obstet Gynecol. 1984;64:151–4. Arumugam K, Lim JM. Menstrual characteristics associated with endometriosis. Br J Obstet Gynecol. 1997;104:948–50. Kruitwagen RFPM, Poels LG, Willemsen WNP, de Ronde IJ, Jap PH, Rolland R. Endometrial epithelial cells in peritoneal fluid during the early follicular phase. Fertil Steril. 1991;55:297–303. Sharpe Timms KL. Endometrial anomalies in women with endometriosis. Ann N Y Acad Sci. 2001;943:131–47. Leyendecker G, Kunz G, Noe M, Herbertz M, Mall G. Endometriosis: a dysfunction and disease of the archimetra. Hum Reprod Update. 1998;4:752–62. Meresman GF, Vighi S, Buquet RA, Contreras-Ortiz O, Tesone M, Rumi LS. Apoptosis and expression of Bcl-2, Bax in eutopic endometrium from women with endometriosis. Fertil Steril. 2000;74:760–6. Aplin AE, Howe A, Alahari SK, Juliano RL. Signal transduction and signal modulation by cell adhesion receptors: the role of integrins, cadherins, immunoglobulin-cell adhesion molecules, and selectins. Pharmacol Rev. 1998;50:197–263. Ballester M, Gonin J, Rodenas A, Bernaudin JF, Rouzier R, Coutant C, Darai E. Eutopic endometrium and peritoneal, ovarian and colorectal endometriotic tissues express a different profile of nectin-1, -3, -4 and nectin-like molecule 2. Hum Reprod. 2012;27:3179–86. Bilotas M, Meresman G, Buquet R, Sueldo C, Baranao RI. Effect of vascular growth factor and interleukin-1β on apoptosis in endometrial cell cultures from patients with endometriosis and controls. J Reprod Immunol. 2010;84:193–8. Cinar O, Seval Y, Uz YH, Cakmak H, Ulukus M, Kayisli UA, Arici A. Differential regulation of Akt phosphorylation in endometriosis. Reprod Biomed Online. 2009;19:864–71. Aghajanova L, Horcajadas JA, Weeks JL, Esteban FJ, Nezhat CN, Conti M, Giudice LC. The protein kinase A pathway-regulated transcriptome of endometrial stromal fibroblasts reveals compromised differentiation and persistent proliferative potential in endometriosis. Endocrinology. 2010;151:1341–55. Kaponis A, Iwabe T, Taniguchi F, Ito M, Deura I, Decavalas G, Terakawa N, Harada T. The role of NF-kappaB in endometriosis. Front Biosci. 2012;4:1213–34. Gonzalez-Ramos R, Van Langendonckt A, Defrere S, Lousse JC, Mettelen M, Guillet A, Donnez J. Agents blocking the nuclear factor-kappaB (NF-κB) pathway are effective inhibitors of endometriosis in an in vivo experimental model. Gynecol Obstet Invest. 2008;65:174–86. Arimoto T, Katagiri T, Oda K, Tsunoda T, Yasugi T, Osuga Y, Yoshikawa H, Nishii O, Yano T, Taketani Y, Nakamura Y. Genome-wide cDNA microarray analysis of gene-expression profiles involved in ovarian endometriosis. Int J Oncol. 2003;22:551–60. Ueda M, Yamashita Y, Takehara M, Terai Y, Kumagai K, Ueki K, Kanda K, Yamaguchi H, Akise D, Hung YC, Ueki M. Survivin gene expression in endometriosis. J Clin Endocrinol Metab. 2002;87:3452–9. Watanabe A, Taniguchi F, Izawa M, Suou K, Uegaki T, Takai E, Terakawa N, Harada T. The role of surviving in the resistance of endometriotic stromal cells to drug-induced apoptosis. Hum Reprod. 2009;24:3172–9. Abe W, Nasu K, Nakada C, Kawano Y, Moriyama M, Narahara H. miR-196b targets c-myc and Bcl-2 expression, inhibits proliferation and induces apoptosis in endometriotic stromal cells. Hum Reprod. 2013;28:750–61. Reis FM, Petraglia F, Taylor RN. Endometriosis: hormone regulation and clinical consequences of chemotaxis and apoptosis. Hum Reprod Update. 2013;19:406–18. Kokawa K, Shikone T, Nakano R. Apoptosis in the human uterine endometrium during the menstrual cycle. J Clin Endocrinol Metabol. 1996;81:4144–7. Vaskivuo TE, Stenback F, Karhumaa P, Risteli J, Dunkel L, Tapanainen JS. Apoptosis and apoptosis-related proteins in human endometrium. Mol Cell Endocrinol. 2000;165:75–83. Watanabe H, Kanzaki H, Narukawa S, Inoue T, Katsuragawa H, Kaneko Y, Mori T. Bcl-2 and Fas expression in eutopic and ectopic human endometrium during the menstrual cycle in relation to endometrial cell apoptosis. Am J Obstet Gynecol. 1997;176:360–8. Rogers PA, Lederman F, Plunkett D, Affandi B. Bcl-2, Fas, and caspase-3 expression in endometrium from levonorgestrel implant users with and without breakthrough bleeding. Hum Reprod. 2000;15:152–61. Chittenden T, Harrington EA, O’Connor R, Flemington C, Lutz RJ, Evan GI, Guild BC. Induction of apoptosis by the Bcl-2 homologue Bak. Nature. 1995;374:731–3. Narkar M, Kholkute S, Chitlange S, Nandedkar T. Expression of steroid hormone receptors, proliferation and apoptotic markers in primate endometrium. Mol Cell Endocrinol. 2006;246:107–13. Tao XJ, Sayegh RA, Tilly JT, Isaacson KB. Elevated expression of the proapoptotic BCL-2 family member, BAK, in the human endometrium coincident with apoptosis during the secretory phase of the cycle. Fertil Steril. 1998;70:338–43. Bilotas M, Baranao RI, Buquet R, Sueldo C, Tesone M, Meresman G. Effects of GnRH analogues on apoptosis and expression of Bcl-2, Bax, Fas, and FasL proteins in endometrial epithelial cell cultures from patients with endometriosis and controls. Hum Reprod. 2007;22:644–53. Peng X, Maruo T, Matsuo H, Takekida S, Deguchi J. Serum deprivation-induced apoptosis in cultures porcine granulosa cells is characterized by increased expression of p53 protein, Fas antigen and Fas ligand and by decreased expression of PCNA. Endocr J. 1998;45:247–53. Abe H, Shibata MA, Otsuki Y. Caspase of Fas-mediated apoptosis in human normal endometrium and endometrial carcinoma cells. Mol Hum Reprod. 2006;12:535–41. Gebel HM, Braun DP, Tambur A, Frame D, Rana N, Dmowski DP. Spontaneous apoptosis of endometrial tissue is impaired in women with endometriosis. Fertil Steril. 1998;9:1042–7. Jones RK, Searle RF, Bulmer JN. Apoptosis and bcl-2 expression in normal human endometrium, endometriosis and adenomyosis. Hum Reprod. 1998;13:3496–502. Fujishita A, Chavez RO, Nakane PK, Yamabe T, Koji T, Ishimau T, Masuzaki H. Expression of estrogen and progesterone receptors in endometrium and peritoneal endometriosis: an immunohistochemical and in situ hybridization study. Fertil Steril. 1997;67:856–64. McLaren J, Prentice A, Charnock-Jones DS, Sharkey AM, Smith SA. Immunocolonization of the apoptosis regulating proteins Bcl-2 and Bax in human endometrium and isolated peritoneal fluid macrophages in endometriosis. Hum Reprod. 1997;12:146–52. Braun DP, Ding J, Shaheen F, Willey JC, Rana N, Dmowski WP. Quantitative expression of apoptosis-regulating genes in endometrium from women with and without endometriosis. Fertil Steril. 2006;87:263–8. Banu SK, Lee JH, Speights VO, Starzinski-Powitz A, Arosh JA. Selective Inhibition of Prostaglandin E2 Receptors EP2 and EP4 Induces Apoptosis of Human Endometriotic Cells through suppression of ERK1/2, Akt, NF_B, and β-Catenin Pathways and activation of intrinsic apoptotic mechanisms. Mol Endocrinol. 2009;23:1291–305. Harada M, Suganuma N, Furuhashi M, Nagasaka T, Nakashima N, Kikkawa F, Tomoda Y, Furui K. Detection of apoptosis in human endometriotic tissues. Mol Hum Reprod. 1996;2:307–15. Eidukaite A, Siaurys A, Tamosiunas V. Aberrant expression of CD95 and CD69 molecules among CD56+ cells in women with endometriosis. Am J Reprod Immunol. 2006;55:276–81. Garcia Velasco JA, Mulayim N, Kayisli UA, Arici A. Elevated soluble Fas ligand levels may suggest a role for apoptosis in women with endometriosis. Fertil Steril. 2002;78:855–9. Garcia Velasco J, Arici A, Zreick T, Naftolin F, Mor G. Macrophage-derived growth factors regulate FasL expression in endometrial stromal cells: a role in endometriosis. Mol Hum Reprod. 1999;5:642–50. Selam B, Kayisli UA, Garcia Velasco JA, Arici A. Extracellular matrix-dependent regulation of Fas ligand expression in human endometrial stromal cells. Biol Reprod. 2002;66:1–5. Kayagaki N, Kawasaki A, Ebata T, Ohmoto H, Ikeda S, Inoue S, Yoshino K, Okumura K, Yagita H. Metalloproteinase-mediated release of human Fas ligand. J Exp Med. 1995;182:1777–83. Harada T, Iwabe T, Terakawa N. Role of cytokines in endometriosis. Fertil Steril. 2001;76:1–10. Iwabe T, Harada T, Tsudo T, Nagano Y, Yoshida S, Tanikawa M, Terakawa N. Tumor necrosis factor-alpha promotes proliferation of endometriotic stromal cells by inducing interleukin-8 gene and protein expression. J Clin Endocrinol Metab. 2000;85:824–9. Selam B, Kayisli UA, Garcia Velasco JA, Akbas GE, Arici A. Regulation of Fas ligand expression by IL-8 in human endometrium. J Clin Endocrinol Metabol. 2002;8:3921–7. Li MQ, Luo XZ, Meng YH, Mei J, Zhu XY, Jin LP, Li DJ. CXCL8 enhances proliferation and growth and reduces apoptosis in endometrial stromal cells in an autocrine manner via a CXCR-triggered PTEN/AKT signal pathway. Hum Reprod. 2012;27:2107–16. Li MQ, Li HP, Meng YH, Wang XQ, Zhu XY, Mei J, Li DJ. Chemokine CCL2 enhances survival and invasiveness of endometrial stromal cells in an autocrine manner by activating Akt and MAPK/Erk1/2 signal pathway. Fertil Steril. 2012;97:919–29. Meresman GF, Bilotas MA, Buquet RA, Baranao R, Sueldo C, Tesone M. Gonadotropin-releasing hormone agonist induces apoptosis and reduces cell proliferation in eutopic endometrial cultures from women with endometriosis. Fertil Steril. 2003;80:702–7. Khan ΚΝ, Kitajima Μ, Hiraki Κ, Fujishita Α, Sekine Ι, Ishimaru Τ, Masuzaki Η. Changes in tissue inflammation, angiogenesis and apoptosis in endometriosis, adenomyosis and uterine myoma after GnRH agonist therapy. Hum Reprod. 2010;25:642–53. Tesone M, Bilotas M, Barañao RI, Meresman G. The role of GnRH analogues in endometriosis-associated apoptosis and angiogenesis. Gynecol Obstet Invest. 2008;66 Suppl 1:10–8. Sakamoto Y, Harada T, Horie S, Iba Y, Taniguchi F, Yoshida S, Iwabe T, Terakawa N. Tumor necrosis factor-a-induced interleukin-8 (IL-8) expression in endometriotic stromal cells, probably through nuclear factor-kappaB activation: gonadotropin-releasing hormone agonist treatment reduced IL-8 expression. J Clin Endocrinol Metabol. 2003;88:730–5. Nasu K, Nishida M, Ueda T, Yuge A, Takai N, Narahara H. Application of the nuclear factor-kappaB inhibitor, BAY 11-7085, for the treatment of endometriosis: an in vitro study. Am J Physiol Endocrinol Metab. 2007;293:E16–23. Suou K, Taniguchi F, Tagashira Y, Kiyama T, Terakawa N, Harada T. Apigenin inhibits tumor necrosis factor α-induced cell proliferation and prostaglandin E2 synthesis by inactivating NFκB in endometriotic stromal cells. Fertil Steril. 2011;95:1518–21. Zhang JJ, Xu ZM, Zhang CM, Dai HY, Ji XQ, Wang XF, Li C. Pyrrolidine dithiocarbamate inhibits nuclear factor-κB pathway activation, and regulates adhesion, migration, invasion and apoptosis of endometriotic stromal cells. Mol Hum Reprod. 2011;17:175–81. Othman EE, Salama S, Ismail N, Al-Hendy A. Toward gene therapy of endometriosis:adenovirus-mediated delivery of dominant negative estrogen receptor genes inhibits cell proliferation, reduces cytokine production, and induces apoptosis of endometriotic cells. Fertil Steril. 2007;88:462–71. Meresman GF, Bilotas M, Abello V, Buquet R, Tesone M, Sueldo C. Effects of aromatase inhibitors on proliferation and apoptosis in eutopic endometrial cell cultures from patients with endometriosis. Fertil Steril. 2005;84:459–63. Harada T, Momoeda M, Taketani Y, Hoshiai H, Terakawa N. Low-dose oral contraceptive pill for dysmenorrhea associated with endometriosis: a placebo-controlled, double-blind, randomized trial. Fertil Steril. 2008;90:1583–8. Meresman GF, Auge L, Baranao RI, Lombardi E, Tesone M, Sueldo C. Oral contraceptives suppress cell proliferation and enhance apoptosis of eutopic endometrial tissue from patients with endometriosis. Fertil Steril. 2002;77:1141–7. Yuan P, Huang Y, Wu H, Teng Z, Zhang J, Xin X. Induction of a local pseudo-pregnancy via levonorgestrel-loaded microspheres for the treatment of endometriosis in a rabbit model. Hum Reprod. 2010;25:462–9. Nasu K, Nishida M, Ueda T, Takai N, Bing S, Narahara H, Miyakawa I. Bufalin induces apoptosis and G0/G1 cell cycle arrest of endometriotic stromal cells a promising agent for treatment of endometriosis. Mol Hum Reprod. 2005;11:817–23. Nishida M, Nasu K, Ueda T, Yuge A, Takai N, Narahara H. Beta-hydroxyisovalerylshikonin induces apoptosis and G0/G1 cell cycle arrest of endometriotic stromal cells preliminary in vitro study. Hum Reprod. 2006;21:2850–6. Altintas D, Kokcu A, Kandemir B, Tosun M, Cetinkaya MB. Comparison of the effects of raloxifene and anastrozole on experimental endometriosis. Eur J Obstet Gynecol Reprod Biol. 2010;150:84–7. Tsuno A, Nasu K, Kawano Y, Yuge A, Li H, Abe W, Narahara H. Fasudil inhibits the proliferation and contractility and induces cell cycle arrest and apoptosis of human endometriotic stromal cells: a promising agent for the treatment of endometriosis. J Clin Endocrinol Metab. 2011;96:E1944–52. Kawano Y, Nasu K, Li H, Tsuno A, Abe W, Takai N, Narahara H. Application of the histone deacetylase inhibitors for the treatment of endometriosis: histone modifications as pathogenesis and novel therapeutic target. Hum Reprod. 2011;26:2486–98. Banu SK, Lee J, Speights Jr VO, Starzinski-Powitz A, Arosh JA. Cyclooxygenase-2 regulates survival, migration and invasion of human endometriotic cells through multiple mechanisms. Endocrinology. 2008;149:1180–9. Author information Authors and Affiliations Corresponding author Editor information Editors and Affiliations Rights and permissions Copyright information © 2014 Springer Japan About this chapter Cite this chapter Kaponis, A., Kollia, G., Taniguchi, F., Harada, T., Decavalas, G. (2014). Apoptosis in Endometriosis. In: Harada, T. (eds) Endometriosis. Springer, Tokyo. https://doi.org/10.1007/978-4-431-54421-0_12 Download citation DOI: https://doi.org/10.1007/978-4-431-54421-0_12 Published: Publisher Name: Springer, Tokyo Print ISBN: 978-4-431-54420-3 Online ISBN: 978-4-431-54421-0 eBook Packages: MedicineMedicine (R0)