Background: Polycystic ovary syndrome (PCOS) is associ-ated with oxidative stress. Cumulus cells (CCs) are biologically differentiated from other follicular cells and have specialized roles in oocyte maturation during folliculogenesis. Reactive oxygen species (ROS) can greatly damage the ovarian follicles and change the expression of oxidative phosphorylation (OX-PHOS) genes. A recent study of granulosa cells by microarray and subsequent qPCR validations revealed overexpression of two OXPHOS genes, neutrophil cytosolic factor 2 (NCF2) and thioredoxin interacting protein (TXNIP) in PCOS with insulin resistance (IR) and/or non-IR.
NCF2 is a rate-limiting cofac-tor of NADPH oxidase, and increased expression of
NCF2 po-tentiates NADPH oxidase activity, leading to oxidative stress.
TXNIP encodes a cytoplasmic protein that inhibits the activity of thioredoxin disulfide reductase and thereby increases oxida-tive stress. Due to lack of data on CCs and their importance in folliculogenesis, we studied expression of NCF2,
TXNIP and succinate dehydrogenase B (SDHB), a high abundant OX-PHOS gene as internal control, in CCs of IR and non-IR PCOS. Materials and Methods: Eight women with PCOS-IR, 8 women with PCOS non-IR based on Rotterdam criteria as case groups and 8 women without PCOS with male factor infertil-ity as control group, all underwent GnRH antagonist protocol treatment at Royan Institute were included in this case-control study. Gene expression of CCs was studied by real time PCR. Normalization was performed considering Hypoxanthine phos-phoribosyltransferase 1 (HPRT1) expression as a tissue specific reference gene based on previous evidences. Kruskal-Wallis was used to compare between groups. All statistical tests were two-sided and P<0.05 was considered statistically significant. Results: Expression of
NCF2 in IR was higher than non-IR and control groups (P=0.005, P=0.002, respectively) with a fold change over 40.
TXNIP was overexpressed in IR compared to controls (P=0.012) with a fold change around 15 while no sig-nificant difference was observed in
SDHB expression, as ex-pected.Conclusion: Overexpression of
NCF2 and
TXNIP genes in CCs of PCOS was in accordance with previous findings in granulosa cells of PCOS. Fold changes of upregulation in CCs were much more than those of previously reported in granulosa cells (2.13-3.32). It seems in CCs of PCOS, response to oxida-tive stress conditions is very stronger than those granulose cells.