steve bAccumulation of nerve growth factor and its receptors in the uterus and dorsal root ganglia in a mouse model of adenomyosis

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.

Proteomic identification of neurotrophins in the eutopic endometrium of women with endometriosis

“…An interesting finding was that only a minority of the NGF migrated as the mature 13 kD isoform, whereas the majority had an apparent mass of 27 kD (Fig. 3A), corresponding to proNGF (29). As expected, levels of β-actin, a housekeeping control protein, were constant in controls and cases.…”

Metformin inhibits growth of eutopic stromal cells from adenomyotic endometrium via AMPK activation and subsequent inhibition of AKT phosphorylation: a possible role in the treatment of adenomyosis

“…Further research is needed using our data to search for other compounds that increase AMPK activation more effectively for treatment of adenomyosis. Interestingly, adenomyosis has been reported to be associated with enhanced expression of nerve growth factor b (Li et al 2011), tyrosine kinase receptor B (Huang et al 2011), and PAK1 (Kim et al 2010), all of which are thought to signal through PI3K. PI3K/AKT signaling plays an important role in cell survival.…”

“…Indeed, the estrogen agonist tamoxifen has been successfully used to generate mouse models of adenomyosis (Li et al 2011). Leyendecker et al (2009) have proposed a tissue injury and repair theory of adenomyosis, in which microtrauma at the endometrial-myometrial junction causes local hyperestrogenism and enhanced peristaltic activity within the zone of the endomyometrial junction.…”

Exposure to the environmental endocrine disruptor TCDD and human reproductive dysfunction: Translating lessons from murine models

“…Adenomyosis, like endometriosis, has been associated with reduced fertility, pelvic pain, heavy menstrual bleeding and dysmenorrhea [5, 101]. The causes of adenomyosis are currently unknown, although both human and animal studies have suggested a role of inflammatory processes in the development of this disease [102–105]. In our murine model, we recently reported the transgenerational occurrence of adenomyosis in mice exhibiting the endometriosis-like uterine phenotype as a consequence of developmental TCDD exposure of F1 animals [102].…”