Endometriosis Research Centre, Department of Gynecology, Charité, Campus Benjamin Franklin, 12200, Berlin, Germany.
Department of Biology, Chemistry, Pharmacy, Freie Universität Berlin, Takustr. 3, 14195, Berlin, Germany.
Mol Neurobiol. 2017 Sep;54(7):5131-5141. doi: 10.1007/s12035-016-0058-1. Epub 2016 Aug 24.
Endometriosis is a chronic inflammatory disease and one of the most common causes of pelvic pain. The mechanisms underlying pain emergence or chronic inflammation during endometriosis remain unknown. Several chronic inflammatory diseases including endometriosis show reduced amounts of noradrenergic nerve fibers. The source of the affected innervation is still unclear. Semaphorins represent potential elicitors, due to their known role as axonal guidance cues, and are suggested as nerve repellent factors in different chronic inflammatory diseases. Therefore, semaphorins might influence the progress of neuroinflammatory mechanisms during endometriosis. Here, we analyzed the noradrenergic innervation and the expression of the specific semaphorins and receptors possibly involved in the neuroimmunomodulation in endometriosis. Our studies revealed an affected innervation and a significant increase of semaphorins and their receptors in peritoneal endometriotic tissue. Thereby, the expression of the receptors was identified on the membrane of noradrenergic nerve fibers and vessels. Macrophages and activated fibroblasts were found in higher density levels and additionally express semaphorins in peritoneal endometriotic tissue. Inflammation leads to an increased release of immune cells, which secrete a variety of inflammatory factors capable of affecting innervation. Therefore, our data suggests that the chronic inflammatory condition in endometriosis might contribute to the increase of semaphorins, which could possibly affect the innervation in peritoneal endometriosis.
子宫内膜异位症是一种慢性炎症性疾病，也是盆腔疼痛的最常见原因之一。子宫内膜异位症中疼痛出现或慢性炎症的发生机制尚不清楚。几种慢性炎症性疾病，包括子宫内膜异位症，显示出去甲肾上腺素能神经纤维的数量减少。受影响的神经支配的来源仍不清楚。信号素代表潜在的诱导物，由于它们作为轴突导向线索的已知作用，并被认为是不同慢性炎症性疾病中的神经排斥因子。因此，信号素可能会影响子宫内膜异位症中神经炎症机制的进展。在这里，我们分析了神经免疫调节中可能涉及的去甲肾上腺素能神经支配以及特定信号素和受体的表达。我们的研究表明，腹膜子宫内膜异位组织中的神经支配受到影响，信号素及其受体的表达显著增加。因此，受体的表达被确定在去甲肾上腺素能神经纤维和血管的膜上。在腹膜子宫内膜异位组织中，巨噬细胞和激活的成纤维细胞的密度水平较高，并且还表达信号素。炎症导致免疫细胞释放增加，这些免疫细胞分泌多种能够影响神经支配的炎症因子。因此，我们的数据表明，子宫内膜异位症中的慢性炎症状态可能导致信号素的增加，这可能会影响腹膜子宫内膜异位症中的神经支配。
