Skip to main content

Advertisement

SpringerLink
Log in

Human Adenomyosis Endometrium Stromal Cells Secreting More Nerve Growth Factor

Impact and Effect

  • Original Article
  • Published:
Reproductive Sciences Aims and scope Submit manuscript

Abstract

Abnormal expression of nerve growth factor (NGF) was found in adenomyosis (AM). We collected AM foci from patients and eutopic endometrium from non-AM controls. Endometrium stromal cells (ESCs) were cultured. Different levels of 17β-estradiol, tumor necrosis factor (TNF), CoCl2, and H2O2 were added to the culture system separately, then the expression level of NGF in ESCs was detected. After adding different levels of NGF, the proliferation and apoptosis of ESCs and aromatase expression were detected. We found that 17β-estradiol promoted NGF production in AM ESCs but not in control ESCs; TNF promoted NGF production in both AM and control ESCs; and CoCl2 inhibited NGF production in control ESCs, but had no effect in AM ESCs. Nerve growth factor promoted the proliferation and synthesis of aromatase in AM ESCs. In conclusion, locally increased estrogen levels and inflammation may cause increased NGF production in the uterus of patients with AM. Nerve growth factor stimulated the proliferation and increased aromatase expression of ESCs from AM foci, suggesting NGF might contribute to the pathology and etiology of AM.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Lee NC, Dicker RC, Rubin GL, Ory HW. Confirmation of the preoperative diagnoses for hysterectomy. Am J Obstet Gynecol. 1984;150(3):283–287.

    Article  CAS  PubMed  Google Scholar 

  2. Pistofidis G, Makrakis E, Koukoura O, Bardis N, Balinakos P, Anaf V. Distinct types of uterine adenomyosis based on laparo-scopic and histopathologic criteria. Clin Exp Obstet Gynecol. 2014;41(2):113–118.

    Article  CAS  PubMed  Google Scholar 

  3. Ferenczy A. Pathophysiology of adenomyosis. Hum Reprod Update. 1998;4(4):312–322.

    Article  CAS  PubMed  Google Scholar 

  4. Maheshwari A, Gurunath S, Fatima F, Bhattacharya S. Adenomyosis and subfertility: a systematic review of prevalence, diagnosis, treatment and fertility outcomes. Hum Reprod Update. 2012;18(4):374–392.

    Article  PubMed  Google Scholar 

  5. Khan KN, Kitajima M, Hiraki K, et al. Changes in tissue inflammation, angiogenesis and apoptosis in endometriosis, adenomyosis and uterine myoma after GnRH agonist therapy. Hum Reprod. 2010;25(3):642–653.

    Article  CAS  PubMed  Google Scholar 

  6. Leyendecker G, Wildt L, Mall G. The pathophysiology of endometriosis and adenomyosis: tissue injury and repair. Arch Gynecol Obstet. 2009;280(4):529–538.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. 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. Fertil Steril. 2013;100(3):801–809.

    Article  CAS  PubMed  Google Scholar 

  8. Huang PC, Tsai EM, Li WF, et al. Association between phthalate exposure and glutathione S-transferase M1 polymorphism in adenomyosis, leiomyoma and endometriosis. Hum Reprod. 2010;25(4):986–994.

    Article  CAS  PubMed  Google Scholar 

  9. Li Y, Zhang S, Xian X, Zou S. Adenomyosis uterine innervation in mice correlates to nerve growth factor expression, inflammation, and vascularization. Neural Regen Res. 2010;5:15–20.

    CAS  Google Scholar 

  10. Goteri G, Lucarini G, Montik N, et al. Expression of vascular endothelial growth factor (VEGF), hypoxia inducible factor1alpha (HIF-1alpha), andmicrovessel density in endometrial tissue in women with adenomyosis. Int J Gynecol Pathol. 2009;28(2):157–163.

    Article  PubMed  Google Scholar 

  11. Anaf V, Simon P, El Nakadi I, et al. Hyperalgesia, nerve infiltration and nerve growth factor expression in deep adenomyotic nodules, peritoneal and ovarian endometriosis. Hum Reprod. 2002;17(7):1895–1900.

    Article  PubMed  Google Scholar 

  12. Anaf V, El Nakadi I, De Moor V, Chapron C, Pistofidis G, Noel JC. Increased nerve density in deep infiltrating endometriotic nodules. Gynecol Obstet Invest. 2011;71(2):112–117.

    Article  CAS  PubMed  Google Scholar 

  13. Anaf V, Chapron C, El Nakadi I, De Moor V, Simonart T, Noël JC. Pain, mast cells, and nerves in peritoneal, ovarian, and deep infiltrating endometriosis. Fertil Steril. 2006;86(5):1336–1343.

    Article  PubMed  Google Scholar 

  14. Levi-Montalcini R. The nerve growth factor 35 years later. Science. 1987;237(4819):154–162.

    Article  Google Scholar 

  15. Petty BG, Cornblath DR, Adornato BT, Chaudhry V, Flexner C, Wachsman M. The effect of systemically administered recombinant human nerve growth factor in healthy human subjects. Ann Neurol. 1994;36(2):244–246.

    Article  CAS  PubMed  Google Scholar 

  16. Malcangio M, Garrett NE, Tomlinson DR. Nerve growth factor treatment increases stimulus-evoked release of sensory neuropeptides in the rat spinal cord. Eur J Neurosci. 1997;9(5):1101–1104.

    Article  CAS  PubMed  Google Scholar 

  17. McMahon SB. NGF as a mediator of inflammatory pain. Philos Trans R Soc Lond B Biol Sci. 1996;351(1338):431–440.

    Article  CAS  PubMed  Google Scholar 

  18. Florenzano F, Bentivoglio M. Degranulation, density, and distribution of mast cells in the rat thalamus: a light and electron microscopic study inbasal conditions and after intracerebroventricular administration of nerve growth factor. J Comp Neurol. 2000;424(4):651–669.

    Article  CAS  PubMed  Google Scholar 

  19. Li Yan, Zhang Shaofen, Xu Linna. Expression of nerve growth factor produced by ectopic endometrium from patients with adenomyosis and its relationship with pain scales and innervation. Zhonghua Fu Chan Ke Za Zhi. 2014;49(2):120–124.

    CAS  PubMed  Google Scholar 

  20. Kobayashi H, Yamada Y, Morioka S, Niiro E, Shigemitsu A, Ito F. Mechanism of pain generation for endometriosis-associated pelvic pain. Arch Gynecol Obstet. 2014;289(1):13–21.

    Article  CAS  PubMed  Google Scholar 

  21. Chen Y, Li D, Zhang Z, Takushige N, Kong BH, Wang GY. Effect of siRNA Against β-NGF on Nerve Fibers of a Rat Model With Endometriosis. Reprod Sci. 2014;21(3):329–339.

    Article  PubMed  CAS  Google Scholar 

  22. Kajitani T, Maruyama T, Asada H, et al. Possible involvement of nerve growth factor in dysmenorrhea and dyspareunia associated with endometriosis. Endocr J. 2013;60(10):1155–1164.

    Article  CAS  PubMed  Google Scholar 

  23. Li Y, Zhang SF, Zou SE, Xia X, Bao L. Accumulation of nerve growth factor and its receptors in the uterus and dorsal root ganglia in a mouse model of adenomyosis. Reprod Biol Endocrinol. 2011;9:30.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Li Y, Zhang S, Xia X, Zou S. Establishment of an ICR mouse modle of adenomyosis by oral administration of tamoxifen. Acta Lab Or Aatorium Animalis Scientia Sinica. 2009;17:346–350.

    Google Scholar 

  25. Parrott E, Butterworth M, Green A, White IN, Greaves P. Adenomyosis–a result of disordered stromal differentiation. Am J Pathol. 2001;159(2):623–630.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Reichardt LF. Neurotrophin-regulated signalling pathways. Philos Trans R Soc Lond B Biol Sci. 2006;361(1473):1545–1564.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Bjorling DE, Beckman M, Clayton MK, Wang ZY. Modulation of nerve growth factor in peripheral organs by estrogen and progesterone. Neuroscience. 2002;110(1):155–167.

    Article  CAS  PubMed  Google Scholar 

  28. Freund-Michel V, Frossard N. The nerve growth factor and its receptors in airway inflammatory diseases. Pharmacol Ther. 2008;117(1):52–76.

    Article  CAS  PubMed  Google Scholar 

  29. Zhang G, Dmitrieva N, Liu Y, McGinty KA, Berkley K. Endometriosis as a neurovascular condition: estrous variations in innervation, vascularization, and growth factor content of ectopic endometrial cysts in the rat. Am J Physiol Regul Integr Comp Physiol. 2008;294(1):R162–R171.

    Article  CAS  PubMed  Google Scholar 

  30. Bulun SE, Fang Z, Imir G, et al. Aromatase and endometriosis. Semin Reprod Med. 2004;22(1):45–50.

    Article  CAS  PubMed  Google Scholar 

  31. Kitawaki J. Adenomyosis: the pathophysiology of an oestrogen-dependent disease. Best Pract Res Clin Obstet Gynaecol. 2006;20(4):493–502.

    Article  PubMed  Google Scholar 

  32. Ishihara H, Kitawaki J, Kado N, Koshiba H, Fushiki S, Honjo H. Gonadotropin-releasing hormone agonist and danazol normalize aromatase cytochrome P450 expression in eutopic endometrium from women with endometriosis, adenomyosis, or leiomyomas. Fertil Steril. 2003;79(suppl 1):735–742.

    Article  PubMed  Google Scholar 

  33. Shi Z, Arai KY, Jin W, et al. Expression of nerve growth factor and its receptors NTRK1 and TNFRSF1B is regulated by estrogen and progesterone in the uteri of golden hamsters. Biol Reprod. 2006;74(5):850–856.

    Article  CAS  PubMed  Google Scholar 

  34. Wang F, Li H, Yang Z, Du X, Cui M, Wen Z. Expression of interleukin-10 in patients with adenomyosis. Fertil Steril. 2009;91(5):1681–1685.

    Article  PubMed  Google Scholar 

  35. Li B, Chen M, Liu X, Guo SW. Constitutive and tumor necrosis factor-α-induced activation of nuclear factor-κB in adenomyosis and its inhibition by andrographolide. Fertil Steril. 2013;100(2):568–577.

    Article  CAS  PubMed  Google Scholar 

  36. Acosta CM, Cortes C, MacPhee H, Namaka MP. Exploring the role of nerve growth factor in multiple sclerosis: implications in myelin repair. CNS Neurol Disord Drug Targets. 2013;12(8):1242–1256.

    Article  CAS  PubMed  Google Scholar 

  37. Aalto K, Korhonen L, Lahdenne P, Pelkonen P, Lindholm D. Nerve growth factor in serum of children with systemic lupus erythematosus is correlated with disease activity. Cytokine. 2002;20(3):136–139.

    Article  CAS  PubMed  Google Scholar 

  38. Seidel MF, Lane NE. Control of arthritis pain with anti-nerve-growth factor: risk and benefit. Curr Rheumatol Rep. 2012;14(6):583–588.

    Article  CAS  PubMed  Google Scholar 

  39. Bonini S, Lambiase A, Lapucci G, et al. Nerve growth factor and asthma. Allergy. 2002;57(suppl 72):13–15.

    Article  PubMed  Google Scholar 

  40. Cheong YC, Shelton JB, Laird SM, et al. IL-1, IL-6 and TNF-alpha concentrations in the peritoneal fluid of women with pelvic adhesions. Hum Reprod. 2002;17(1):69–75.

    Article  CAS  PubMed  Google Scholar 

  41. Kuno R, Yoshida Y, Nitta A, Nabeshima T, Wang J, Sonobe Y. The role of TNF-alpha and its receptors in the production of NGF and GDNF by astrocytes. Brain Res. 2006;1116(1):12–18.

    Article  CAS  PubMed  Google Scholar 

  42. Wang B, Trayhurn P. Acute and prolonged effects of TNF-alpha on the expression and secretion of inflammation-related adipo-kines by human adipocytes differentiated in culture. Pflugers Arch. 2006;452(4):418–427.

    Article  CAS  PubMed  Google Scholar 

  43. Emanueli C, Salis MB, Pinna A, Graiani G, Manni L, Madeddu P. Nerve growth factor promotes angiogenesis and arteriogenesis in ischemic hindlimbs. Circulation. 2002;106(17):2257–2262.

    Article  CAS  PubMed  Google Scholar 

  44. Rende M, Brizi E, Conner J, et al. Nerve growth factor (NGF) influences differentiation and proliferation of myogenic cells in vitro via TrKA. Int J Dev Neurosci. 2000;18(8):869–885.

    Article  CAS  PubMed  Google Scholar 

  45. Schnegelsberg B, Sun TT, Cain G, et al. Overexpression of NGF in mouse urothelium leads to neuronal hyperinnervation, pelvic sensitivity, and changes in urinary bladder function. Am J Physiol Regul Integr Comp Physiol. 2010;298(3):R534–R547.

    Article  CAS  PubMed  Google Scholar 

  46. Qi H, Li DQ, Shine HD, et al. Nerve growth factor and its receptor TrkA serve as potential markers for human corneal epithelial progenitor cells. Exp Eye Res. 2008;86(1):34–40.

    Article  CAS  PubMed  Google Scholar 

  47. Yang JH, Wu MY, Chen CD, Chen MJ, Yang YS, Ho HN. Altered apoptosis and proliferation in endometrial stromal cells of women with adenomyosis. Hum Reprod. 2007;22(4):945–952.

    Article  CAS  PubMed  Google Scholar 

  48. Othumpangat S, Gibson LF, Samsell L, Piedimonte G. NGF is an essential survival factor for bronchial epithelial cells during respiratory syncytial virus infection. PLoS One. 2009;4(7):e6444.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  49. Kendall TJ, Hennedige S, Aucott RL, et al. p75 Neurotrophin receptor signaling regulates hepatic myofibroblast proliferation and apoptosis in recovery from rodent liver fibrosis. Hepatology. 2009;49(3):901–910.

    Article  CAS  PubMed  Google Scholar 

  50. Attar E, Tokunaga H, Imir G, et al. Prostaglandin E2 via steroidogenic factor-1 coordinately regulates transcription of steroidogenic genes necessary for estrogen synthesis in endometriosis. J Clin Endocrinol Metab. 2009;94(2):623–631.

    Article  CAS  PubMed  Google Scholar 

  51. Marshall JS, Gomi K, Blennerhassett MG, Bienenstock J. Nerve growth factor modifies the expression of inflammatory cytokines by mast cells via a prostanoid-dependent mechanism. J Immunol. 1999;162(7):4271–4276.

    CAS  PubMed  Google Scholar 

  52. Quinn MJ. Endometriosis: the consequence of uterine denervation-reinnervation. Arch Gynecol Obstet. 2011;284(6):1423–1429.

    Article  PubMed  Google Scholar 

  53. Hefti FF, Rosenthal A, Walicke PA, Wyatt S, Vergara G, Shelton DL, Davies AM. Novel class of pain drugs based on antagonism of NGF. Trends Pharmacol Sci. 2006;27(2):85–91.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Gynaecology, Obstetrics and Gynaecology Hospital, Fudan University, Shanghai, 200011, China

    Yan Li PhD, Shien Zou PhD, Xian Xia PhD & Shaofen Zhang MD

  2. Reproductive Medicine Center, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China

    Yan Li PhD

Authors
  1. Yan Li PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shien Zou PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xian Xia PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Shaofen Zhang MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Shaofen Zhang MD.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Li, Y., Zou, S., Xia, X. et al. Human Adenomyosis Endometrium Stromal Cells Secreting More Nerve Growth Factor. Reprod. Sci. 22, 1073–1082 (2015). https://doi.org/10.1177/1933719114561559

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1177/1933719114561559

Keywords

Search

Navigation