Dewanto Agung, Dudas Jozsef, Glueckert Rudolf, Mechsner Sylvia, Schrott-Fischer Anneliese, Wildt Ludwig, Seeber Beata
Department of Gynecological Endocrinology and Reproductive Medicine, Medical University of Innsbruck, Anichstrasse 35, Innsbruck, 6020, Austria.
Department of Obstetrics and Gynecology, Gadjah Mada University, Yogyakarta, Indonesia.
Reprod Biol Endocrinol. 2016 Aug 12;14(1):43. doi: 10.1186/s12958-016-0178-5.
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.
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.
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).
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.
神经营养因子神经生长因子（NGF）和脑源性神经营养因子（BDNF）在神经元生长和发育中的作用已为人所知。同时，神经营养因子受体酪氨酸激酶A（TrkA）、TrkB和p75对决定细胞命运很重要。在子宫内膜异位症中，这个复杂的系统尚未完全阐明。本研究的目的是评估这些神经营养因子及其受体在腹膜（PE）和深部浸润性子宫内膜异位症（DIE）组织中的表达和定位，并测量和比较疾病亚型中神经纤维的密度。
用抗BDNF、-NGF、-TrkA、-TrkB、-p75、蛋白基因产物9.5（PGP9.5，完整神经纤维）和酪氨酸羟化酶（TH，交感神经纤维）抗体对PE病变（n = 20）和DIE病变（n = 22）进行免疫染色，并在连续切片上进行分析。
PE和DIE中BDNF阳性免疫染色细胞的百分比同样高（大于75%）。仅在基质中，TrkB（主要的BDNF受体）和p75在DIE中的免疫染色细胞百分比高于PE（分别为p < 0.014，p < 0.027）。与PE病变相比，DIE病变的腺体和基质中NGF阳性免疫染色细胞的百分比均较低（分别为p < 0.01和p < 0.01），但DIE病变中TrkA的免疫染色没有显著降低。PE（26.27±17.32）和DIE（28.19±33.15，p = 0.8）中PGP9.5染色的神经纤维平均密度没有差异。当我们进行亚组分析时，肠道DIE中的神经密度（平均57.33±43.9）显著高于PE（平均26.27±17.32，p < 0.01）和非肠道DIE（平均14.6±8.6，p < 0.002）。
虽然神经营养因子BDNF在PE和DIE中同样存在，但其受体TrkB和p75在DIE中表达更高，可能在DIE的病理生理学中具有潜在作用，特别是在促进细胞生长方面。BDNF与p75受体的结合亲和力比NGF更强，可能在DIE中诱导交感神经轴突修剪，导致神经纤维密度降低。
