Nitric oxide mediated activation of adrenomedullin and matrix metalloproteinases-2 and -9 in women with endometriosis undergoing IVF

Abstract

Adrenomedullin (ADM), a vasodilator peptide, is reported to participate in the growth and differentiation of the endometrium. Its function is mediated at least partly by nitric oxide (NO). Association of intrafollicular concentration of ADM in women with endometriosis undergoing IVF is not reported so far. The aim of the present study is to examine NO mediated activation of ADM and matrix metalloproteinases (MMP) -2 and -9 in women with endometriosis undergoing IVF. Follicular fluid (FF) was collected from 80 women with endometriosis and 50 normal ovulating women with tubal factor infertility (controls) at the time of oocyte retrieval. These women were reporting to the Institute of Reproductive Medicine, Kolkata, India for IVF treatment. All women were of age between 26 and 38 years. Expression of ADM, MMP-2 and -9 in FF was assessed using Western blot and their quantitative analysis done by ELISA. Total nitrite level, measured as an index of NO, was measured using spectrophotometry. Intrafollicular levels of NO, ADM, MMP-2 and MMP-9 were found to be significantly higher in endometriosis as compared to controls. A significant positive correlation was observed between NO level and expression of ADM (r = 0.491, P<0.0001), MMP-2 (r = 0.602, P<0.0001) and MMP-9 (r = 0.758, P<0.0001), respectively. In addition, IVF outcome parameters were adversely affected in endometriosis compared with controls. The findings suggest that increased NO level in endometriosis activates the production of ADM and MMPs which promote angiogenesis and excessive matrix degradation, respectively. While NO, MMP-2 and -9 correlated well with IVF outcome, no relationship existed between FF concentrations of ADM and IVF success rate. Drug induced regulation of NO may be considered as a potential option for improving IVF outcome in endometriosis.