Abstract

BackgroundAdenomyosis is a common gynecological disease, which is accompanied by a series of immunological and neuroendocrinological changes. Nerve growth factor (NGF) plays a critical role in producing pain, neural plasticity, immunocyte aggregation and release of inflammatory factors. This study aimed to investigate the expression of NGF and its two receptors in uteri and dorsal root ganglia (DRG) in an adenomyosis mouse model, as well as their relationship with the severity of adenomyosis.MethodsForty newborn ICR mice were randomly divided into the adenomyosis model group and control group (n = 20 in each group). Mice in the adenomyosis model group were orally dosed with 2.7 μmol/kg tamoxifen on days 2-5 after birth. Experiments were conducted to identify the expression of NGF- beta and its receptors, tyrosine kinase receptor (trkA) and p75 neurotrophin receptor (p75NTR), in the uterus and DRG in four age groups (90+/-5 d, 140+/-5 d, 190+/-5 d and 240+/-5 d; n = 5 mice in each group) by western bolt, immunochemistry and real time reverse transcription-polymerase chain reaction.ResultsAdenomyosis, which became more serious as age increased, was successfully induced in dosed ICR mice. NGF-beta, trkA and p75NTR protein levels in the uterus and trkA mRNA levels in DRG were higher in the older aged adenomyosis model group than those in controls (190+/-5 d and 240+/-5 d groups, P < 0.05). The expression of NGF-beta and its receptors in the uterus increased gradually as age increased for adenomyosis mice (190+/-5 d and 240+/-5 d, P < 0.05, compared with 90+/-5 d) but it showed little change in control mice. The mRNA level of trkA in DRG also increased as age increased in the adenomyosis model group (190+/-5 d and 240+/-5 d, P < 0.05, compared with 90+/-5 d) but was unchanged in controls. The mRNA level of p75NTR in DRG was not different between the adenomyosis and control groups and was stable from young to old mice.ConclusionsNGF- beta can be used as an indicator for the severity of adenomyosis. The gradually increasing level of NGF- beta and its receptors while the disease becomes more severe suggests an effect of NGF- beta on pathogenic mechanisms of adenomyosis.

Highlights

  • Adenomyosis is a common gynecological disease, which is accompanied by a series of immunological and neuroendocrinological changes

  • The receptors of Nerve growth factor (NGF) are high-affinity tyrosine kinase receptor and low-affinity p75 neurotrophin receptor (p75NTR), and they are immunoreactive in nerve fibers that are close to endometriotic glands and blood vessels [13,14,15]

  • By examining the protein and mRNA levels of NGF and its receptors in the uterus and dorsal root ganglia (DRG) at different ages in adenomyosis mice, we aimed to evaluate any changes with the severity of adenomyosis in peripheral organs and the central nerve system

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Summary

Introduction

Adenomyosis is a common gynecological disease, which is accompanied by a series of immunological and neuroendocrinological changes. Nerve growth factor (NGF) plays a critical role in producing pain, neural plasticity, immunocyte aggregation and release of inflammatory factors. Adenomyosis is defined as the presence of ectopic endometrial glands and stroma within the myometrium It is a relatively frequent endomyometrial pathology that is found in multiparous women between 40 and 50 years of age [1]. NGF was the first neurotrophic factor to be discovered and it plays a critical role in producing pain, neural plasticity, immunocyte aggregation, and release of inflammatory factors [6,7]. Several studies have suggested that abnormal expression of NGF in adenomyosis and endometriosis might be involved in the pathomechanism of these diseases [8,9,10]. Abnormal expression of the nonfunctional subunit NGF-a (not the functional subunit NGFb) has been detected in uteri of newborn mice, which acquire adenomyosis in adulthood [16,17]

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