Nerve Fibers are Absent in Disease-Free and Eutopic Endometrium, but Present in Endometriotic (Especially Deep) Lesions

Abstract

Objective Detection of nerve fibers in endometrial biopsies was recently proposed as a noninvasive diagnostic tool for endometriosis. However, their occurrence in the functional layer of endometrium still remains controversial. Nerve fibers were found to be present in endometriotic lesions themselves, which may account for some of the pain experienced by patients, but their origin is not clear. The objective of the present study was to reevaluate the presence of nerve fibers in endometrium and in different types of endometriotic lesions. Patients and Methods Nerve fiber density (PGP9.5 immunohistochemical analysis), unmyelinated nerve fiber presence (neurofilament immunohistochemical detection) and nerve growth factor expression were evaluated in endometrial (disease free: n = 20; endometriotic: n = 26) and endometriotic (peritoneal lesions: n = 11; ovarian lesions: n = 16; rectovaginal lesions: n = 27) samples. Results Endometrial biopsies were found to be mostly negative for nerve fibers. Nerve fiber density was higher in deep nodular lesions than in peritoneal (p<0.01) or ovarian (p<0.001) lesions. Around 30% of PGP9.5-positive nerve fibers were confirmed by neurofilament staining. Nerve growth factor expression was detected at higher levels in the stroma of deep-infiltrating lesions (p<0.05). Conclusions No nerve fibers were detected in endometrial biopsies (from healthy or endometriosis patients). However, nerve fibers were detected in endometriotic lesions. Most of them were found to be unmyelinated, suggesting they could be implicated in pain. Deep nodular lesions may be more neuroattractive through the action of nerve growth factor.