Increased concentration of 8-hydroxy-2′-deoxyguanosine in follicular fluid of infertile women with endometriosis

Abstract

Impaired oocyte quality and oxidative stress might be involved in the pathogenesis of endometriosis-related infertility. To improve our understanding of the role of oxidative stress in this condition, we compare eight oxidative stress markers from each stage, including the simultaneous analysis of lipids, proteins and DNA damage, in the serum and follicular fluid of infertile women with endometriosis and infertile controls undergoing controlled ovarian stimulation for intracytoplasmic sperm injection. In total, 87 serum samples (43 with endometriosis, 44 controls) and 61 follicular fluid samples (29 with endometriosis, 32 controls) free of blood contamination upon visual inspection and presenting granulosa cells alone or granulosa cells plus a retrieved mature oocyte were collected on the day of oocyte retrieval. Total hydroperoxides, malondialdehyde, advanced oxidation protein products, glutathione, superoxide dismutase (SOD) and total antioxidant capacity (TAC) were determined by spectrophotometry, vitamin E by high-performance liquid chromatography and 8-hydroxy-2'-deoxyguanosine (8OHdG) by enzyme-linked immunosorbent assay. The endometriosis group showed higher serum concentrations of glutathione and SOD, lower serum concentrations of TAC and higher follicular concentrations of 8OHdG and vitamin E compared with infertile controls. These data indicate both systemic and follicular oxidative stress in infertile patients with endometriosis. For the first time, we demonstrate the presence of oxidative DNA damage, represented by higher 8OHdG concentrations in the follicular microenvironment of these patients, possibly related to compromised oocyte quality and associated with the pathogenesis of endometriosis-related infertility.

Implications of immune dysfunction on endometriosis associated infertility

“…Similarly, high concentrations of oxidative stress molecules and low levels of antioxidative molecules have been found in the follicular fluid from women with endometriosis. Singh et al detected higher levels of ROS, NOS and MDA in the follicular fluid of women with endometriosis and another study detected an increased concentration of 8-hydroxy-2’-deoxyguanosine, a metabolite of DNA oxidative damage, in the follicular fluid of specifically infertile women with endometriosis [91, 92]. In addition, the concentrations of critical antioxidants are aberrantly expressed in endometriosis patients.…”

Iron overload and altered iron metabolism in ovarian cancer

“…In particular, follicular fluid contains hormones such as estradiol (Emori and Drapkin, 2014), reactive oxygen species (ROS), and transferrin (Shigeta et al, 2016). Additionally, iron and DNA adducts are increased in follicular fluid of endometriosis patients compared to infertile controls (Singh et al, 2013; Da Broi et al, 2016). Iron and transcript levels of ferritin and transferrin receptor were increased in follicles close to an endometrioma (characterized by elevated iron levels (Yamaguchi et al, 2008)) affecting oocyte retrieval (Sanchez et al, 2014) although another study did not identify any differences in iron content or ferritin levels (Benaglia et al, 2015).…”

Is the oocyte quality affected by endometriosis? A review of the literature

“…In this context, the presence of an increase oxidative stress status in the FF, has been recently confirmed in follicles surrounding an endometrioma - using proteomics by mass spectrometry [33]– and has been proposed as the culprit of spindle disruption. Accordingly, Da Broi et al found an increase follicular 8-hydroxy-2′-deoxyguanosine, an indicator of oxidative DNA damage, in the FF of women with both mild and severe endometriosis [34, 35]. Among other factors, also brain-derived neurotrophic factor (BDNF) has been implicated as a molecular link between protection from oxidative stress and folliculogenesis [36, 37].…”