Higher SOD1 Gene Expression in Cumulus Cells From Infertile Women With Moderate and Severe Endometriosis

Abstract

It is questioned whether worsening of oocyte quality and oxidative stress (OS) are involved in the pathogenesis of infertility related to endometriosis and in compromised intracytoplasmic sperm injection (ICSI) outcomes. Cumulus cells (CCs) protect oocytes from entering apoptosis induced by OS. Thus, we carried out a case-control study comparing expression of superoxide dismutase 1 (SOD1), superoxide dismutase 2 (SOD2), and glutathione peroxidase 4 (GPX4; genes encoding for the main antioxidant enzymes) in CCs from mature oocytes of 26 infertile patients with minimal/mild endometriosis, 14 patients with moderate/severe endometriosis, and 41 controls undergoing controlled ovarian stimulation for ICSI, using real-time polymerase chain reaction. As a secondary objective, we investigated the interaction between the expression of these genes and clinical pregnancy (CP) by a statistical model. Only infertile women with moderate/severe endometriosis showed increased expression of the SOD1 in CCs compared to women with minimal/mild endometriosis and controls, with a positive interaction between increased expression and the occurrence of CP, suggesting that SOD1 might be a potential biomarker of CP following ICSI.

Single-cell analysis of differences in transcriptomic profiles of oocytes and cumulus cells at GV, MI, MII stages from PCOS patients

“…Higher expression of NOS can cause LH to stimulate the proliferation of CCs48. Recent research showed higher SOD1 gene expression in CCs in infertile women, which could be a biomarker of clinical pregnancy after Intra-Cytoplasmic Sperm Injection (ICSI)49. Expression of the PLA2G4A gene is regulated by LH/hCG-dependent induction in granular cells via the adenylyl cyclase/cAMP pathway; therefore, lower expression of PLA2G4A in PCOS CCs reflected an abnormal LH surge50.…”

Single-cell RNA sequencing of oocytes from ovarian endometriosis patients reveals a differential transcriptomic profile associated with lower quality

“…Interestingly, several studies also report that women with endometriosis have high levels of oxidative stress markers and low levels of antioxidant markers in serum (Lambrinoudaki et al, 2009;Prieto et al, 2012) and follicular fluid (Singh et al, 2013;Nasiri et al, 2017), suggesting increased oxidative stress in these patients (Nakagawa et al, 2016). Recently, altered oxidative stress in the follicular fluid of women with endometriosis was proposed to have a negative impact in folliculogenesis, affecting apoptosis, damaging DNA in GCs and cumulus cells (Goud et al, 2014;Donabela et al, 2015), and potentially altering oocyte development. Accordingly, follicular fluid from women with endometriosis, when applied to bovine and murine oocytes, promotes meiotic abnormalities such as chromosomic instability and spindle abnormalities (Choi et al, 2007;Mansour et al, 2010;Da Broi et al, 2014), implying a connection between oxidative stress and cell cycle.…”

Antioxidative enzyme-related gene expression levels in cumulus cells during in vitro fertilization: A comparison between normal and poor ovarian responders

“…Sample size calculation was analyzed according to the previous study by Donabela et al [13] with mean of SOD1 relative gene expression in healthy women control group; 2.06 2 -Δ ΔCT (SD = 0.53). To compare two different means, the sample size calculation was performed with the following expectation; SOD1 gene expression level in POR was lower than NOR by 20%, resulting in a number of 25 women for each study group.…”