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

Objective To evaluate neurotrophin (NT) expression in the endometrium of women with and without endometriosis. Design Prospective, cross-sectional, translational study. Setting Academic hospital. Patient(s) Thirty-three reproductive-age women undergoing laparoscopy for infertility, pelvic pain, intramural fibroids, or tubal ligation. Intervention(s) Endometrial biopsies, protein microarrays, reverse transcriptase–polymerase chain reaction, ELISAs, and Western blotting. Main Outcome Measure(s) Neurotrophin proteins and mRNAs in eutopic endometrial biopsies. Result(s) Among seven neurotrophic proteins detected on the antibody microarrays, reverse transcriptase–polymerase chain reaction analysis confirmed nerve growth factor, NT-4/5, and brain-derived neurotrophic factor mRNAs in endometrial tissue. Quantitative ELISAs revealed that NT-4/5 (806 ± 701 vs. 256 ± 190 pg/100 mg protein) and brain-derived neurotrophic factor (121 ± 97 vs. 14 ± 11 ng/100 mg protein) concentrations were significantly higher in women with endometriosis. Nerve growth factor (100 ± 74 vs. 93 ± 83 pg/100 mg protein) levels did not differ between cases and controls. Conclusion(s) Neurotrophins are synthesized in situ within the endometrium. NT-4/5 and brain-derived neurotrophic factor proteins were more concentrated in biopsies from endometriosis cases than controls, whereas nerve growth factor levels were similar. We hypothesize that the local production of NTs induces sensory innervation of endometrium of women with endometriosis. These NTs represent novel targets for the diagnosis and treatment of endometriosis.