Characterization of endometriosis-associated nerve fibers and their properties

Endometriosis is an estrogen dependent chronic inflammatory gynecological disease associated with painfull conditions. We could already demonstrate endometriosis associated  nerve fibres. The nervous system has an influence on the pathogenesis of chronic inflammatory diseases. The sympathetic nervous system exerts an anti-inflammatory effect, while the sensory nervous system promotes, through a stimulation of immune cells, pro-inflammatory changes. This is reflected in a reduced density of sympathetic nerve fibers in inflammatory tissue, but an increased density of sensory nerve fibers in endometriosis. Nerve fibres in peripheral regions distal of the endometriotic lesion are as well altered. The nervous system seems to play an important role in the pain pathology in endometriosis and further characterisations are needed.

Projects

  • Sensory and sympathetic innervation with neurotransmitter expression analysis in various different manifestations of endometriosis
  • the role of calcium-binding proteins in endometriosis
  • Vanilloid, serotonin and µ-opioid receptors in the pain transmission of endometriosis associated pain
  • estrogen receptor expression on nerve fibres

Investigations of the neuroimmunomodulatory properties of endometriosis

Nerve fibers seem to play an important role in the development of endometriosis associated pain. It seems to be possible that EM itself modulates the peritoneal innervation. We could demonstrate nerve fibres as well as neurotrophins closely associated with peritoneal endometriotic lesions. Furthermore, the peritoneal fluid of patients with EM seems to be involved in neuroimmunemodulatory effects. EM-associated neuroimmunomodulatory effects seem to be to due a complex interaction of several factors. Not only the altered nerve fibre densities, with a preponderance of sensory proinflammatory neurotransmitters in endometriosis seem to lead to a further activation of nociceptors and to an reinforced inlammatory response but prostaglandins, Interleukins as well as activated immune competent cells and neurotrophins contribute to a permanent hyperacivation of nociceptors and to a hyperalgesia in endometriosis patients.

Projects

  • Characterisation of Neurotrophins (NGF, BDNF, NT-3/4/5) in peritoneal lesions and in the lesion surrounding peritoneal fluid
  • Interaktion of Neurotrophins and pro-inflammatory cytokines with nerve fibres in endometriosis
  • In vitro analysis of neuromodulatory factors (like Neurotrophins, estrogen and semaphorins) with chicken embryonic ganglia and neuronal cell cultures
  • Pain transmission in an endometriosis-mouse-model

Characterization of endometriosis-associated smooth muscle cells and their properties

Another focus of our research is the characterization of endometriosis-associated smooth muscle cells in various forms of endometriosis. We could demonstrate oxytocin receptor (OTR)-positive muscle cells in peritoneal endometriotic lesions. In further studies, we could reveal data supporting a metaplastic origin of these muscle cells. This is particularly important for understanding of the pathogenesis of this disease and pain sensations that could possibly be caused by contraction of peritoneal muscles can be suggested. The detection of morphological changes in the structure of the myometrial wall in adenomyosis highlights the contractile dysfunction in patients with adenomyosis. Also interesting is the observation of a transition of the basal layer into the adjacent myometrium in women with adenomyosis compared to patients without adenomyosis and supports the current theory of rupture due to a basal hyperperistalsis. The OTR is involved in the uterine peristalsis and thus represents a possible  approach in the treatment of dysmenorrhea.

Projects

  • Characterization of endometriosis-associated muscle cells and their properties
  • Studies of endometriosis-associated muscle cell induction
  • Ultrastructural analysis of the basal layer
  • Gene expression analysis of endometriosis-associated smooth muscle cells

Studies on the occurrence of endometriotic cells in lymph nodes of patients with endometriosis and research on lymphangiogenesis

Why and how endometrium-like tissue is implanted outside the uterine cavity is still not clear. One possible mechanism could be the spread of cells via the lymphatic system. We could demonstrate evidence of a lymphatic spread of endometriosis cells via the lymphatic vessels close to endometriotic lesions for the first time . We could as well show endometriotic lesions in pelvic sentinel lymph nodes. The following systematic analysis revealed the occurrence of endometriotic cells in randomly taken lymph nodes. Nodal endometriosis lesions occur with an incidence of 33%, whereas disseminated endometriotic cells are present in up to 83% of the lymph nodes. Perhaps this is an important indicator of an immunological disorder in the sense of a defective degradation of these cells in the lymph nodes. Lymphangiogenesis seems to be induced  in endometriotic lesions which is an entirely new aspect in the pathogenesis of endometriosis. This deserves further investigations.

Projects

  • Investigations on the occurrence of endometriosis cells in lymph nodes of patients with endometriosis
  • Studies of lymphangiogenesis in endometriosis
  • Characterization of invasion factors