Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Reproductive Biology and Endocrinology
Published in: Reproductive Biology and Endocrinology 1/2016

Open Access 01-12-2016 | Research

Localization of TrkB and p75 receptors in peritoneal and deep infiltrating endometriosis: an immunohistochemical study

Authors: Agung Dewanto, Jozsef Dudas, Rudolf Glueckert, Sylvia Mechsner, Anneliese Schrott-Fischer, Ludwig Wildt, Beata Seeber

Published in: Reproductive Biology and Endocrinology | Issue 1/2016

Login to get access

Abstract

Background

The roles of the neurotrophins NGF (Neurotrophic growth factor) and BDNF (brain-derived neurotrophic factor) in neuronal growth and development are already known. Meanwhile, the neurotrophin receptors TrkA (tropomyosin related kinase A), TrkB, and p75 are important for determining the fate of cells. In endometriosis, this complex system has not been fully elucidated yet. The aim of this study was to evaluate the expression and location of these neurotrophins and their receptors in peritoneal (PE) and deep infiltrating endometriotic (DIE) tissues and to measure and compare the density of nerve fibers in the disease subtypes.

Methods

PE lesions (n = 20) and DIE lesions (n = 22) were immunostained and analyzed on serial slides with anti-BDNF, −NGF, −TrkA, −TrkB, −p75,-protein gene product 9.5 (PGP9.5, intact nerve fibers) and -tyrosine hydroxylase (TH, sympathetic nerve fibers) antibodies.

Result

There was an equally high percentage (greater than 75 %) of BDNF-positive immunostaining cells in both PE and DIE. TrkB (major BDNF receptor) and p75 showed a higher percentage of immunostaining cells in DIE compared to in PE in stroma only (p < 0.014, p < 0.027, respectively). Both gland and stroma of DIE lesions had a lower percentage of NGF-positive immunostaining cells compared to those in PE lesions (p < 0.01 and p < 0.01, respectively), but there was no significant reduction in immunostaining of TrkA in DIE lesions. There was no difference in the mean density of nerve fibers stained with PGP9.5 between PE (26.27 ± 17.32) and DIE (28.19 ± 33.15, p = 0.8). When we performed sub-group analysis, the density of nerves was significantly higher in the bowel DIE (mean 57.33 ± 43.9) than in PE (mean 26.27 ± 17.32, p < 0.01) and non-bowel DIE (mean 14.6. ± 8.6 p < 0.002).

Conclusions

While the neurotrophin BDNF is equally present in PE and DIE, its receptors TrkB and p75 are more highly expressed in DIE and may have a potential role in the pathophysiology of DIE, especially in promotion of cell growth. BDNF has a stronger binding affinity than NGF to the p75 receptor, likely inducing sympathetic nerve axonal pruning in DIE, resulting in the lower nerve fiber density seen.
Appendix
Available only for authorised users
Literature
1.
2.
Koninckx PR, et al. Deeply infiltrating endometriosis is a disease whereas mild endometriosis could be considered a non-disease. Ann N Y Acad Sci. 1994;734:333–41.CrossRefPubMed
3.
Tosti C, et al. Pathogenetic Mechanisms of Deep Infiltrating Endometriosis. Reprod Sci. 2015;22(9):1053–9.CrossRefPubMed
4.
5.
Mckinnon BD, et al. Inflammation and nerve fiber interaction in endometriotic pain. Trends Endocrinol Metab. 2015;26(1):1–10.CrossRefPubMed
6.
Mechsner S, et al. Oxytocin receptor expression in smooth muscle cells of peritoneal endometriotic lesions and ovarian endometriotic cysts. Fertil Steril. 2005;83 Suppl 1:1220–31.CrossRefPubMed
7.
Arnold J, et al. Neuroimmunomodulatory alterations in non-lesional peritoneum close to peritoneal endometriosis. Neuroimmunomodulation. 2013;20(1):9–18.CrossRefPubMed
8.
Wang G, et al. Rich innervation of deep infiltrating endometriosis. Hum Reprod. 2009;24(4):827–34.CrossRefPubMed
9.
Barcena De Arellano ML, et al. Evidence of neurotrophic events due to peritoneal endometriotic lesions. Cytokine. 2013;62(2):253–61.CrossRefPubMed
10.
11.
12.
Tarjanne S, et al. Use of hormonal therapy is associated with reduced nerve fiber density in deep infiltrating, rectovaginal endometriosis. Acta Obstet Gynecol Scand. 2015;94(7):693–700.CrossRefPubMed
13.
Anaf V, et al. Hyperalgesia, nerve infiltration and nerve growth factor expression in deep adenomyotic nodules, peritoneal and ovarian endometriosis. Hum Reprod. 2002;17(7):1895–900.CrossRefPubMed
14.
Arnold J, et al. Imbalance between sympathetic and sensory innervation in peritoneal endometriosis. Brain Behav Immun. 2012;26(1):132–41.CrossRefPubMed
15.
Kuteken FS, et al. Expression of neurotrophic and inflammatory mediators in rectosigmoid endometriosis. Rev Bras Ginecol Obstet. 2012;34(12):568–74.CrossRefPubMed
16.
Barcena De Arellano ML, et al. Eutopic endometrium from women with endometriosis does not exhibit neurotrophic properties. J Neuroimmunol. 2012;249(1–2):49–55.CrossRefPubMed
17.
Wessels JM, et al. Estrogen induced changes in uterine brain-derived neurotrophic factor and its receptors. Hum Reprod. 2015;30(4):925–36.CrossRefPubMed
18.
Wessels JM, et al. Assessing brain-derived neurotrophic factor as a novel clinical marker of endometriosis. Fertil Steril. 2016;105(1):119–28.CrossRefPubMed
19.
Liang Y, Yao S. Potential role of estrogen in maintaining the imbalanced sympathetic and sensory innervation in endometriosis. Mol Cell Endocrinol. 2016;424:42–9.CrossRefPubMed
20.
21.
Wessels JM, et al. The brain-uterus connection: brain derived neurotrophic factor (BDNF) and its receptor (Ntrk2) are conserved in the mammalian uterus. PLoS One. 2014;9(4), e94036.CrossRefPubMedPubMedCentral
22.
Gallo G, Lefcort FB, Letourneau PC. The trkA receptor mediates growth cone turning toward a localized source of nerve growth factor. J Neurosci. 1997;17(14):5445–54.PubMed
23.
Brady R, et al. BDNF is a target-derived survival factor for arterial baroreceptor and chemoafferent primary sensory neurons. J Neurosci. 1999;19(6):2131–42.PubMed
24.
Lentz SI, et al. Neurotrophins support the development of diverse sensory axon morphologies. J Neurosci. 1999;19(3):1038–48.PubMed
25.
26.
Leyendecker G, Wildt L. A new concept of endometriosis and adenomyosis: tissue injury and repair (TIAR). Horm Mol Biol Clin Investig. 2011;5(2):125–42.PubMed
27.
Tokushige N, et al. Effect of progestogens and combined oral contraceptives on nerve fibers in peritoneal endometriosis. Fertil Steril. 2009;92(4):1234–9.CrossRefPubMed
28.
Barcena De Arellano ML, et al. Neurotrophin expression is not affected in uteri of women with adenomyosis. J Mol Neurosci. 2012;47(3):495–504.CrossRefPubMed
29.
Kajitani T, et al. Possible involvement of nerve growth factor in dysmenorrhea and dyspareunia associated with endometriosis. Endocr J. 2013;60(10):1155–64.CrossRefPubMed
30.
Indo Y. Neurobiology of pain, interoception and emotional response: lessons from nerve growth factor-dependent neurons. Eur J Neurosci. 2014;39(3):375–91.CrossRefPubMed
31.
Farinas I, et al. Regulation of neurogenesis by neurotrophins in developing spinal sensory ganglia. Brain Res Bull. 2002;57(6):809–16.CrossRefPubMed
32.
Barcena De Arellano ML, Mechsner S. The peritoneum—an important factor for pathogenesis and pain generation in endometriosis. J Mol Med (Berl). 2014;92(6):595–602.
33.
Lagadec C, et al. TrkA overexpression enhances growth and metastasis of breast cancer cells. Oncogene. 2009;28(18):1960–70.CrossRefPubMed
34.
Davidson B, et al. Altered expression and activation of the nerve growth factor receptors TrkA and p75 provide the first evidence of tumor progression to effusion in breast carcinoma. Breast Cancer Res Treat. 2004;83(2):119–28.CrossRefPubMed
35.
36.
37.
Furness JB. The enteric nervous system: normal functions and enteric neuropathies. Neurogastroenterol Motil. 2008;20 Suppl 1:32–8.CrossRefPubMed
38.
Su HC, et al. Dual intrinsic and extrinsic origins of CGRP- and NPY-immunoreactive nerves of rat gut and pancreas. J Neurosci. 1987;7(9):2674–87.PubMed
39.
Oh JT, et al. Morphometric evaluation of PGP9.5 and NCAM expressing nerve fibers in colonic muscle of patients with Hirschsprung’s disease. Yonsei Med J. 2002;43(1):31–6.CrossRefPubMed
40.
Southwell BR, et al. Decrease in nerve fibre density in human sigmoid colon circular muscle occurs with growth but not aging. Neurogastroenterol Motil. 2010;22(4):439–45. e106.CrossRefPubMed
41.
Tomita T. Localization of nerve fibers in colonic polyps, adenomas, and adenocarcinomas by immunocytochemical staining for PGP 9.5. Dig Dis Sci. 2012;57(2):364–70.CrossRefPubMed
42.
Sams VR, et al. Evaluation of PGP9.5 in the diagnosis of Hirschsprung’s disease. J Pathol. 1992;168(1):55–8.CrossRefPubMed
43.
Ferrero S, et al. Loss of sympathetic nerve fibers in intestinal endometriosis. Fertil Steril. 2010;94(7):2817–9.CrossRefPubMed
44.
Singh KK, et al. Developmental axon pruning mediated by BDNF-p75NTR-dependent axon degeneration. Nat Neurosci. 2008;11(6):649–58.CrossRefPubMed
45.
Krizsan-Agbas D, et al. Oestrogen regulates sympathetic neurite outgrowth by modulating brain derived neurotrophic factor synthesis and release by the rodent uterus. Eur J Neurosci. 2003;18(10):2760–8.CrossRefPubMed
46.
Brauer MM, et al. The role of NGF in pregnancy-induced degeneration and regeneration of sympathetic nerves in the guinea pig uterus. J Auton Nerv Syst. 2000;79(1):19–27.
47.
Walker RA. Quantification of immunohistochemistry—issues concerning methods, utility and semiquantitative assessment I. Histopathology. 2006;49(4):406–10.CrossRefPubMed
48.
49.
Taylor CR, Levenson RM. Quantification of immunohistochemistry—issues concerning methods, utility and semiquantitative assessment II. Histopathology. 2006;49(4):411–24.CrossRefPubMed
Metadata
Title
Localization of TrkB and p75 receptors in peritoneal and deep infiltrating endometriosis: an immunohistochemical study
Authors
Agung Dewanto
Jozsef Dudas
Rudolf Glueckert
Sylvia Mechsner
Anneliese Schrott-Fischer
Ludwig Wildt
Beata Seeber
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Reproductive Biology and Endocrinology / Issue 1/2016
Electronic ISSN: 1477-7827
DOI
https://doi.org/10.1186/s12958-016-0178-5

Other articles of this Issue 1/2016

Reproductive Biology and Endocrinology 1/2016 Go to the issue

Review

Relationship between Advanced Glycation End Products and Steroidogenesis in PCOS

Research

Local intra-uterine Ang-(1–7) infusion attenuates PGE2 and 6-keto PGF1α in decidualized uterus of pseudopregnant rats

Research

Characterization of exosomal release in bovine endometrial intercaruncular stromal cells

Research

Assisted reproductive technology pregnancy complications are significantly associated with endometriosis severity before conception: a retrospective cohort study

Short communication

45,X product of conception after preimplantation genetic diagnosis and euploid embryo transfer: evidence of a spontaneous conception confirmed by DNA fingerprinting

Short communication

Experimental and bioinformatic analysis of cultured Bovine Endometrial Cells (BEND) responding to interferon tau (IFNT)