Alteration in the intrafollicular thiol–redox system in infertile women with endometriosis

Abstract

The aim of this study was to compare intrafollicular biomarkers of thiol-redox system and chronic inflammation in infertile patients with and without endometriosis, and examine correlations between biomarkers and IVF outcomes. The study included 65 patients receiving IVF: 31 patients with endometriosis vs 34 patients without endometriosis. Follicular fluid (FF) was obtained from a single-dominant follicle during oocyte retrieval and stored at K70 8C. Malondialdehyde, superoxide dismutase, glutathione (GSH), glutathione peroxidase 3 (GPX3), thioredoxin (TRX), TRX-binding protein 2 (TBP2), and peroxiredoxin-4 levels were measured in the FF samples by ELISAs as biomarkers of oxidative stress. The inflammatory cytokines interleukin 1 beta (IL1b), IL6, IL8, and tumor-necrosis factor alpha (TNFa) were also measured by ELISAs. GSH levels were significantly lower in the endometriosis group compared with the controls. TBP2 levels were significantly higher in the endometriosis group. IL6, IL8, and TNFa levels were significantly higher in the endometriosis group. The levels of all of the inflammatory cytokines positively correlated with the levels of TRX. GSH levels positively correlated with the number of high-quality embryos. GPX3 and TRX levels negatively correlated with the percentage of mature oocytes. TNFa levels negatively correlated with the cumulative embryo score per embryo. Logistic regression analysis revealed that the number of high-quality embryos was an independent factor predicting clinical pregnancy. In conclusion, there may be an imbalance in the thiol-redox system and increased levels of inflammatory cytokines in the intrafollicular microenvironment of infertile patients with endometriosis, which may affect the qualities of the oocyte and embryo. Reproduction (2015) 149 155-162

Implications of immune dysfunction on endometriosis associated infertility

“…In addition, the concentrations of critical antioxidants are aberrantly expressed in endometriosis patients. Levels of glutathione are diminished in the follicular fluid of women with endometriosis [93] and low levels of other antioxidants including vitamin A, C and E were found to be significantly reduced in the intra-follicular fluid of women with endometriosis associated infertility compared to women with tubal infertility [92]. As expected, higher levels of glutathione have been correlated with higher quality embryos [93].…”

“…Levels of glutathione are diminished in the follicular fluid of women with endometriosis [93] and low levels of other antioxidants including vitamin A, C and E were found to be significantly reduced in the intra-follicular fluid of women with endometriosis associated infertility compared to women with tubal infertility [92]. As expected, higher levels of glutathione have been correlated with higher quality embryos [93]. Correspondingly, high concentrations of oxidative stress metabolites and lower concentrations of antioxidant molecules are associated with less successful IVF treatments [92].…”

MECHANISMS IN ENDOCRINOLOGY: Nutrition as a mediator of oxidative stress in metabolic and reproductive disorders in women

“…Furthermore, endogenous antioxidant compounds are also disrupted in women suffering from endometriosis. Specifically, lower plasma SOD concentration, lower follicular fluid vitamin C levels and imbalanced intrafollicular thiolredox system were detected in infertile women with endometriosis, in comparison with controls (207,208). In a study by Mier-Cabrera et al, when a high-antioxidant diet was administered in women with endometriosis, peripheral oxidative stress markers, including MDA and lipid hydroperoxides, were significantly attenuated and antioxidant markers, specifically SOD and GPx, were enhanced (209).…”

Intrafollicular inflammatory cytokines but not steroid hormone concentrations are increased in naturally matured follicles of women with proven endometriosis

“…The custom-designed six-plex kit included reagents to detect human cytokines IL-1β, IL-6, IL-8, IL-15, IL-18 and tumour necrosis factor-α (TNF-α). We have chosen these cytokines as previous studies have shown dysregulation of these factors in endometriosis in serum [6], peritoneal [9] and follicular fluid of conventional, gonadotropin-stimulated IVF [6,[16][17][18], suggesting these factors to be associated with endometriosis. The Bio-Plex® assay was performed according to the manufacturer's instructions and has previously been described [13].…”