Aberrant invasion of nervous fibers in endometriosis: the role of estrogens

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Endometriosis is a complex and heterogeneous disease with unknown etiology. Estrogens, innervation and dysregulation of macrophages are important factors affecting the pathogenesis of pain associated with endometriosis. The aim of the review is to show the role of estrogen in the interaction between macrophages and nerve fibers by polarizing macrophages as a potentially valuable therapeutic target for the treatment of pain in endometriosis. The PubMed database was searched using relevant keywords to identify studies on the role of estrogen in aberrant invasion of nerve fibers in endometriosis. The coexistence of macrophages and nerve fibers induces innovative neuroimmune communications under the influence of estrogens. Persistent stimulation of nerve fiber nociceptors by inflammatory cytokines from macrophages aggravates neuroinflammation by releasing inflammatory neurotransmitters. This neuroimmune interaction, regulated by estrogens, sensitizes peripheral nerves, leading to neuropathic pain in endometriosis. Estrogens can promote the secretion of chemokines from peripheral nerves, enhancing the recruitment and polarization of macrophages in the tissues of the eutopic and ectopic endometrium. Macrophages play a role in activating multiple nerve growth factors that mediate neurogenesis imbalance depending on estrogen.

Keywords:

endometriosis

estrogens

macrophages

nerve fibers

neuroinflammation

Authors:

Burlev V.A.

Nauchnyĭ tsentr akusherstva, ginekologii i perinatologii im. akad. V.I. Kulakova, Moskva

List of references:

Mehedintu C, Plotogea MN, Ionescu S, Antonovici M. Endometriosis still a challenge. 2014;7(3):349-357.
Taylor HS, Giudice LC, Lessey BA, Abrao MS, Kotarski J, Archer DF, Diamond MP, Surrey E, Johnson NP, Watts NB, Gallagher JC, Simon JA, Carr BR, Dmowski WP, Leyland N, Rowan JP, Duan WR, Ng J, Schwefel B, Thomas JW, Jain RI, Chwalisz K. Treatment of endometriosis-associated pain with Elagolix, an Oral GnRH Antagonist. 2017;377(1): 28-40.
Dunselman GA, Vermeulen N, Becker C, Calhaz-Jorge C, D’Hooghe T, De Bie B, Heikinheimo O, Horne AW, Kiesel L, Nap A, Prentice A, Saridogan E, Soriano D, Nelen W; European Society of Human Reproduction and Embryology. ESHRE guideline: management of women with endometriosis. 2014;29(3):400-412.
Johnson NP, Hummelshoj L, Adamson GD, Keckstein J, Taylor HS, Abrao MS, Bush D, Kiesel L, Tamimi R, Sharpe-Timms KL, Rombauts L, Giudice LC; World Endometriosis Society Sao Paulo Consortium. World endometriosis society consensus on the classification of endometriosis. 2017;32(2):315-324.
Chen P, Wang DB, Liang YM. Evaluation of estrogen in endometriosis patients: regulation of GATA-3 in endometrial cells and effects on Th2 cytokines. 2016;42(6):669-677.
Tokushige N, Markham R, Russell P, Fraser IS. Nerve fibres in peritoneal endometriosis. 2006;21(11):3001-3007.
Laux-Biehlmann A, D’Hooghe T, Zollner TM. Menstruation pulls the trigger for inflammation and pain in endometriosis. 2015;36(5):270-276.
Zhu TH, Ding SJ, Li TT, Zhu LB, Huang XF, Zhang XM. Estrogen is an important mediator of mast cell activation in ovarian endometriomas. 2018;155(1):73-83.
Tran LV, Tokushige N, Berbic M, Markham R, Fraser IS. Macrophages and nerve fibres in peritoneal endometriosis. 2009;24(4):835-841.
Capobianco A, Rovere-Querini P. Endometriosis, a disease of the macrophage. 2013;4:9. . eCollection 2013.
Scheerer C, Bauer P, Chiantera V, Sehouli J, Kaufmann A, Mechsner S. Characterization of endometriosis-associated immune cell infiltrates (EMaICI). 2016; 294(3):657-664.
Greaves E, Temp J, Esnal-Zufiurre A, Mechsner S, Horne AW, Saunders PT. Estradiol is a critical mediator of macrophage-nerve cross talk in peritoneal endometriosis. 2015;185(8):2286-2297.
Galvankar M, Singh N, Modi D. Estrogen is essential but not sufficient to induce endometriosis. 2017;42(2): 251-263.
Prossnitz ER, Barton M. Estrogen biology: new insights into GPER function and clinical opportunities. 2014;389(1-2):71-83.
Izawa M, Taniguchi F, Harada T. Molecular background of estrogen receptor gene expression in endometriotic cells. 2016;23(7):871-876.
Burns KA, Thomas SY, Hamilton KJ, Young SL, Cook DN, Korach KS. Early endometriosis in females is directed by immune-mediated estrogen receptor alpha and IL-6 cross-talk. 2018;159(1):103-118.
Burlev VA, Ilyasova NA. The response of progesterone and estrogen nuclear receptors to pregnancy in patients with endometriosis. 2018;24(2):88-96. (In Russ.).
Colon-Caraballo M, Garcia M, Mendoza A, Flores I. Human endometriosis tissue microarray reveals site-specific expression of estrogen receptors, progesterone receptor, and Ki67. 2019;27(7):491-500.
Montagna P, Capellino S, Villaggio B, Remorgida V, Ragni N, Cutolo M, Ferrero S. Peritoneal fluid macrophages in endometriosis: correlation between the expression of estrogen receptors and inflammation. 2008;90(1):156-164.
Han SJ, Jung SY, Wu SP, Hawkins SM, Park MJ, Kyo S, Qin J, Lydon JP, Tsai SY, Tsai MJ, DeMayo FJ, O’Malley BW. Estrogen receptor beta modulates apoptosis complexes and the Inflammasome to drive the pathogenesis of endometriosis. 2015;163(4):960-974.
Moberg C, Bourlev V, Ilyasova N, Olovsson M. Levels of oestrogen receptor, progesterone receptor and αB-crystallin in eutopic endometrium in relation to pregnancy in women with endometriosis. 2015;18(1):30-37.
Moberg C, Bourlev V, Ilyasova N, Olovsson M. Endometrial expression of LIF and its receptor and peritoneal fluid levels of IL-1a and IL-6 in women with endometriosis are associated with the probability of pregnancy. 2015; 292(2):429-437.
Barcena de Arellano ML, Oldeweme J, Arnold J, Schneider A, Mechsner S. Remodeling of estrogen-dependent sympathetic nerve fibers seems to be disturbed in adenomyosis. 2013;100(3):801-809.
Martineti V, Picariello L, Tognarini I, Carbonell SS, Gozzini A, Azzari C, Mavilia C, Tanini A, Falchetti A, Fiorelli G, Tonelli F, Brandi ML. ERbeta is a potent inhibitor of cell proliferation in the HCT8 human colon cancer cell line through regulation of cell cycle components. 2005;12(2):455-469.
Monica BM, Smith PG. Estrogen and female reproductive tract innervation: cellular and molecular mechanisms of autonomic neuroplasticity. 2015;187:1-17.
Greaves E, Collins F, Esnal-Zufiaurre A, Giakoumelou S, Horne AW, Saunders PT. Estrogen receptor (ER) agonists differentially regulate neuroangiogenesis in peritoneal endometriosis via the repellent factor SLIT3. 2014;155(10):4015-4026.
Rowan MP, Berg KA, Roberts JL, Hargreaves KM, Clarke WP. Activation of estrogen receptor alpha enhances bradykinin signaling in peripheral sensory neurons of female rats. 2014;349(3):526-532.
Ahn SH, Monsanto SP, Miller C, Singh SS, Thomas R, Tayade C. Pathophysiology and immune dysfunction in endometriosis. 2015;795976.
Cutolo M, Villaggio B, Bisso A, Sulli A, Coviello D, Dayer JM. Presence of estrogen receptors in human myeloid monocytic cells (THP-1 cell line). 2001;12(2):368-372.
Campbell L, Emmerson E, Williams H, Saville CR, Krust A, Chambon P, Mace KA, Hardman MJ. Estrogen receptor-alpha promotes alternative macrophage activation during cutaneous repair. 2014;134(9):2447-2457.
Kumar P, Sharma A. Gonadotropin-releasing hormone analogs: understanding advantages and limitations. 2014;7(3):170-174.
Zhao Y, Gong P, Chen Y, Nwachukwu JC, Srinivasan S, Ko C, Bagchi MK, Taylor RN, Korach KS, Nettles KW, Katzenellenbogen JA, Katzenellenbogen BS. Dual suppression of estrogenic and inflammatory activities for targeting of endometriosis. 2015;7(271):271-279.
Alvarez P, Bogen O, Levine JD. Role of nociceptor estrogen receptor GPR30 in a rat model of endometriosis pain. 2014;155(12): 2680-2686.
Poirier AA, Cote M, Bourque M, Morissette M, Di Paolo T, Soulet D. Neuroprotective and immunomodulatory effects of raloxifene in the myenteric plexus of a mouse model of Parkinson’s disease. 2016;48:61-71.
Shapouri-Moghaddam A, Mohammadian S, Vazini H, Taghadosi M, Esmaeili SA, Mardani F, Seifi B, Mohammadi A, Afshari JT, Sahebkar A. Macrophage plasticity, polarization and function in health and disease. 2018;233(9):6425-6440.
Wang Y, Fu Y, Xue S, Ai A, Chen H, Lyu Q, Kuang Y. The M2 polarization of macrophage induced by fractalkine in the endometriotic milieu enhances invasiveness of endometrial stromal cells. 2014; 7(1):194-203.
Pinho-Ribeiro FA, Baddal B, Haarsma R, O’Seaghdha M, Yang NJ, Blake KJ, Portley M, Verri WA, Dale JB, Wessels MR, Chiu IM. Blocking Neuronal Signaling to Immune Cells Treats Streptococcal Invasive Infection. 2018;173(5):1083-1097.e22.
Tofaris GK, Patterson PH, Jessen KR, Mirsky R. Denervated Schwann cells attract macrophages by secretion of leukemia inhibitory factor (LIF) and monocyte chemoattractant protein-1 in a process regulated by interleukin-6 and LIF. 2002;22(15):6696-6703.
Simeoli R, Montague K, Jones HR, Castaldi L, Chambers D, Kelleher JH, Vacca V, Pitcher T, Grist J, Al-Ahdal H, Wong LF, Perretti M, Lai J, Mouritzen P, Heppenstall P, Malcangio M. Exosomal cargo including microRNA regulates sensory neuron to macrophage communication after nerve trauma. 2017; 8(1):1778.
Liang Y, Yao S. Potential role of estrogen in maintaining the imbalanced sympathetic and sensory innervation in endometriosis. 2016;424:42-49.
Kanda N, Watanabe S. 17Beta-estradiol enhances the production of nerve growth factor in THP-1-derived macrophages or peripheral blood monocyte-derived macrophages. 2003;121(4):771-780.
Khan N, Smith MT. Neurotrophins and neuropathic pain: role in pathobiology. 2015;20(6):10657-10688.
Kohn J, Aloyz RS, Toma JG, Haak-Frendscho M, Miller FD. Functionally antagonistic interactions between the TrkA and p75 neurotrophin receptors regulate sympathetic neuron growth and target innervation. 1999;19(13):5393-5408.
Liang Y, Wang W, Huang J, Tan H, Liu T, Shang C, Liu D, Guo L, Yao S. Potential role of Semaphorin 3A and its receptors in regulating aberrant sympathetic innervation in peritoneal and deep infiltrating endometriosis. 2015;10(12):e146027.
Scheerer C, Frangini S, Chiantera V, Mechsner S. Reduced sympathetic innervation in endometriosis is associated to Semaphorin 3C and 3F expression. 2017;54(7):5131-5141.
Richeri A, Chalar C, Martinez G, Greif G, Bianchimano P, Brauer MM. Estrogen up-regulation of semaphorin 3F correlates with sympathetic denervation of the rat uterus. 2011;164(1-2):43-50.
Steinthorsdottir V, Thorleifsson G, Aradottir K, Feenstra B, Sigurdsson A, Stefansdottir L, Kristinsdottir AM, Zink F, Halldorsson GH, Munk NN, Geller F, Melbye M, Gudbjartsson DF, Geirsson RT, Thorsteinsdottir U, Stefansson K. Common variants upstream of KDR encoding VEGFR2 and in TTC39B associate with endometriosis. 2016;7:12350.
Long JB, Jay SM, Segal SS, Madri JA. VEGF-A and Semaphorin3A: modulators of vascular sympathetic innervation. 2009;334(1):119-132.
Cattin AL, Burden JJ, Van Emmenis L, Mackenzie FE, Hoving JJ, Garcia CN, Guo Y, McLaughlin M, Rosenberg LH, Quereda V, Jamecna D, Napoli I, Parrinello S, Enver T, Ruhrberg C, Lloyd AC. Macrophage-induced blood vessels guide Schwann cell-mediated regeneration of peripheral nerves. 2015;162(5):1127-1139.
Barcena de Arellano ML, Mechsner S. The peritoneum — an important factor for pathogenesis and pain generation in endometriosis. 2014;92(6):595-602.
Burlev VA, Ilyasova NA. The density of nervous fiber and nucleus isoforms expression of estrogen and progesterone receptors in eutopic endometrium in patients with peritoneal endometriosis: pregnancy outcomes. 2014;20(6):61-69. (In Russ.).
Bohonyi N, Pohoczky K, Szalontai B, Perkecz A, Kovacs K, Kajtar B, Orban L, Varga T, Szegedi S, Bodis J, Helyes Z, Koppán M. Local upregulation of transient receptor potential ankyrin 1 and transient receptor potential vanilloid 1 ion channels in rectosigmoid deep infiltrating endometriosis. 2017;13:2071457956.
Jung H, Toth PT, White FA, Miller RJ. Monocyte chemoattractant protein-1 functions as a neuromodulator in dorsal root ganglia neurons. 2008;104(1):254-263.
Burlev VA, Ilyasova NA. Neuroangiogenesis in endometrium of women with endometriosis and chronic pelvic pain: high expression of vasoactive intestinal peptide. Probl2017;23(4):87-97. (In Russ.).
Bourlev V, Moberg Ch, Ilyasova N, Davey E, Kallak ThK, Olovsson M. Vasoactive intestinal peptide is upregulated in women with endometriosis and chronic pelvic pain. 2018;80(3):e12857.

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