Correlation between 21 amino acid endothelin, intrafollicular steroids and follicle size in stimulated cycles

Abstract

Several in-vitro studies have shown that endothelins (ET) may inhibit synthesis of progesterone and prevent luteinization of granulosa cells. In the present study, a specific radioimmunoassay was used to evaluate the correlation between concentrations of active (21 residue) ET and ovarian steroids in 47 samples of human follicular fluid (FF) following gonadotrophin stimulation for in-vitro fertilization (IVF) protocols. An isoform non-selective antibody was used in the radioimmunoassay, which recognized the C-terminal structure of the 21 residue ET, and therefore did not crossreact with their weakly active precursors - big ET. In pooled samples of follicular fluid (FF), the concentration of 21 amino acid ET correlated negatively with diameter of the follicles (r = -0.31, P < 0.05) and progesterone concentrations in FF (r = -0.56, P < 0. 001). A positive relationship (non-significant) was found between ET and testosterone concentrations. No correlation between ET and oestradiol was observed. The within-patient correlation coefficients were also evaluated in women from whom three or more samples of FF were obtained. ET were markedly inversely correlated with follicle size in all cases, and with progesterone in five of seven women. Five of seven patients also showed significant positive correlation of ET with testosterone. The results demonstrate clinical evidence that active ET play an important role in regulation of follicle development, especially in the inhibition of premature luteinization of granulosa cells.

The level of vascular endothelial cell growth factor, nitric oxide, and endothelin-1 was correlated with ovarian volume or antral follicle counts: A potential predictor of pregnancy outcome in IVF

“…Our data showed a reduction in ET-1 concentration in the women who became pregnant following IVF. Some studies suggest that there was a negative correlation between the concentration of ET-1 in follicular fluid and in the number of oocytes retrieved or with AFC (Haq et al 1996) and the maturation of follicles (Plonowski et al 1999). Consistent with these studies, our data also showed that the concentration of ET-1 in follicular fluid was negatively correlated with AFC or ovary volume.…”

Altered endothelin expression in granulosa-lutein cells of women with polycystic ovary syndrome

“…Their levels in the follicular fluid are significantly higher than their levels in the serum (Choi et al, 2011), suggesting that endothelins are produced endogenously. However, their levels from hyper-stimulated IVF patients are too scattered and thus endothelins are not suitable as a biomarker for the ovulation process (Plonowski et al, 1999). Therefore, we evaluated their expression levels in the GLCs.…”

“…Endothelial cells produce endothelins, but endothelin-1 is also expressed in ovarian cells and the peptide is present in the follicular fluid of normal women (Magini et al, 1996;Mancina et al, 1997;Iwai et al, 1993). Moreover, the concentration of endothelin-1 is negatively correlated with follicle diameter (Plonowski et al, 1999). Another endothelin peptide was recently shown to have an important ovarian function: produced by the granulosa cells around the time of ovulation, endothelin-2 affects follicular rupture and corpus luteum formation (Ko et al, 2006;Klipper et al, 2010).…”

From global proteome profiling to single targeted molecules of follicular fluid and oocyte: contribution to embryo development and IVF outcome

“…Human [152] a-1-antitrypsin Over-expression leads to decrease oocyte quality Human [153,154] Vascular endothelial growth factor (VEGF) Over-expression leads to decrease oocyte quality and fertilization rate Human [155] Leptin Over-expression leads to decrease oocyte quality and fertilization rate Human [156][157][158] Endothelin-2 Increase oocyte maturation and fertilization rate Human [159,160] Homocystein Over-expression leads to decrease oocyte quality Human [161,162] Lactoferrin Increase oocyte quality, fertilization and cleavage rate Human [163] D-aspartic acid Increase fertilization rate Human [164] Prorenin Decrease fertilization rate Human [165] Heparan sulfate proteoglycan perlecan (HSPG) Oocyte quality, increase fertilization rate and growth factor binding and apoptosis regulation Human [59, 166,167] Fibronectin-binding protein A Cell adhesion and fertilization Human Amphiregulin, heparan sulfate proteoglycan 2; tumor necrosis factor a induced protein 6 (TNFAIP6); plasminogen, lymphatic vessel endothelial hyaluronan receptor 1, a-1-microglobulin/ bikuninprecursor (AMBP), SERPINA1, apolipoprotein A1 (APOA1) and haptoglobin (HP)…”