Expression of neuronal markers in the endometrium of women with and those without endometriosis

Newman, T.A., Bailey, J.L., Stocker, L.J., Woo, Y.L., Macklon, N.S. and Cheong, Y.C. (2013) Expression of neuronal markers in the endometrium of women with and those without endometriosis. Human Reproduction, 28 (9), 2502-2510. (doi:10.1093/humrep/det274). (PMID:23820422)

Abstract

STUDY QUESTION How do the expression patterns of neuronal markers differ in the endometrium of women with and without endometriosis?

SUMMARY ANSWER The neuronal markers, PGP9.5, NGFp75 and VR1, are expressed in the endometrium at levels that do not differ between women with and without endometriosis.

WHAT IS KNOWN ALREADY Aberrant neuronal growth within the uterus may contribute to abnormal fertility and uterine dysfunction. However, controversy still exists as to whether aberrant innervation in the endometrium is associated with gynaecological pathology such as endometriosis. This may reflect the use of subjective methods such as histology to assess the innervation of the endometrium. We, therefore, employed a quantitative method, western blotting, to study markers of endometrial innervation in the presence and absence of endometriosis.

STUDY DESIGN, SIZE, DURATION This study included 45 women undergoing laparoscopic examination for the diagnosis of endometriosis. Endometrial samples were analysed by western blot for the expression of neuronal and neurotrophic markers, PGP9.5, VR1 and NGFp75.

PARTICIPANTS/MATERIALS, SETTINGS, METHODS Endometrial pipelle biopsies were obtained from patients with (n = 20, study group) and without (n = 25, control group) endometriosis. Tissue was analysed by immunohistochemistry and western blot analysis for the expression of pan-neuronal marker, PGP9.5, sensory nociceptive marker, TPVR1, and low-affinity neurotrophic growth factor receptor, NGFRp75.

MAIN RESULTS AND THE ROLE OF CHANCE PGP9.5, NGFp75 and VR1 were expressed in the endometrium of women, independent of the presence of endometriosis. Furthermore, the expression level of PGP9.5, VR1 and NGFp75 did not alter between the two cohorts of women.

LIMITATIONS, REASONS FOR CAUTION Studies of this nature are subject to the heterogeneous nature of patient population and tissue samples despite attempts to standardize these parameters. Hence, further studies using similar methodology will be required to confirm our results.

WIDER IMPLICATIONS OF THE FINDINGS Our results highlight that sensory neuronal markers are present in women with and without endometriosis. Future work will assess what the targets of the endometrial nerves are and investigate their function, their impact on endometrial biology and, in particular, whether aberrant neuronal function, rather than the mere presence of neuronal function, could be the root cause of subfertility and/or pain affecting many endometriosis sufferers. Our results do not, however, confirm the previous paradigm of increased innervation in the endometrium of women with endometriosis, nor the use of nerve cell detection from pipelle biopsies to diagnose endometriosis.

STUDY FUNDING/COMPETING INTEREST(S) This work was funded by the Infertility Research Trust (IRT) and the University of Malaya. There are no competing interests.

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Contributors

Author: T.A. Newman

Author: Y.C. Cheong

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