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Reproduction Abstracts (2014) 1 P006 | DOI: 10.1530/repabs.1.P006


Estrogen-dependent modulation of neuroinflammation in endometriosis

Erin Greaves, Andrew W Horne & Philippa T K Saunders


University of Edinburgh, Edinburgh, UK.

Introduction: Endometriosis is an estrogen-dependent inflammatory disorder, associated with debilitating pelvic pain. We believe the pain is due to neuroinflammation: growth of sensory neurons and their subsequent hypersensitisation by macrophage-derived cytokines within the lesion. We explored the regulation of neuroinflammation by estrogen receptor (ER) modulators.

Materials and methods: Peritoneum and lesions were collected from women with and without endometriosis and from a novel MacGreen (transgenic Cfs1r-EGFP) mouse model of endometriosis. Immunofluorescence was used to locate macrophages and nerves, and QPCR to measure macrophage-derived cytokines (IL6, IL1β, and TNFα). Human peripheral blood monocyte derived macrophages and mice with endometriosis were exposed to ER agonists.

Results and discussion: IL6 and IL1β mRNAs were elevated in peritoneum and lesions of women with pain or endometriosis (P<0.05) compared to women without disease. Levels were reduced (P<0.05) in women taking oral contraceptives/GnRH analogues. IL6 and TNFα correlated with pain scores in women with pain but no endometriosis (P<0.05 and P<0.01), highlighting the importance of cytokines in pelvic pain, and a possible role for estrogenic manipulation. In mice with endometriosis, macrophage chemotactic ligands were elevated (P<0.001) in lesions compared to peritoneum. Using MacGreen mice we identified macrophages originating from peritoneum and shed endometrium. IL1β and TNFα were elevated (P<0.001) in mouse lesions and exposure of mice to DPN (ERβ agonist) abrogated this effect. In isolated macrophages IL1β and IL6 were estrogen-regulated. Macrophages and nerve fibres were closely associated in mouse lesions. Modulation of ERs may reduce neuroinflammation in lesions and offer a new opportunity to manage endometriosis-associated pain.

Volume 1

World Congress of Reproductive Biology 2014

Edinburgh, UK
02 Sep 2014 - 04 Sep 2014

World Congress of Reproductive Biology 

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