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.
AugouleaAAlexandrouACreatsaMVrachnisNLambrinoudakiI. Pathogenesis of endometriosis: the role of genetics, inflammation and oxidative stress. Arch Gynecol Obstet. 2012;286(1):99–103.
2.
DonnezJSquiffletJPirardCJadoulPWynsCSmetsM. The efficacy of medical and surgical treatment of endometriosis-associated infertility and pelvic pain. Gynecol Obstet Invest. 2002;54(suppl 1):2–10.
3.
HolochKJLesseyBA. Endometriosis and Infertility. Clin Obstet Gynecol. 2010;53(2):429–438. 410.1097/GRF.1090b1013e3181db1097d1071.
4.
de ZieglerDBorgheseBChapronC. Endometriosis and infertility: pathophysiology and management. Lancet. 2010;376(9742):730–738.
5.
BarnhartKDunsmoor-SuRCoutifarisC. Effect of endometriosis on in vitro fertilization. Fertil Steril. 2002;77(6):1148–1155.
6.
AboulgharMMansourRSerourGAl-InanyH. Diagnosis and management of unexplained infertility: an update. Arch Gynecol Obstet. 2003;267(4):177–188.
7.
Al-FadhliR KSTulandiTTanrSL. Effects of different stages of endometriosis on the outcome of in vitro fertilization. J Obstet Gynaecol Can. 2006;28(10):888–891.
8.
LinXWeiMTongX. Outcome of in vitro fertilization in endometriosis-associated infertility: a 5-year database cohort study. Chin Med J (Engl). 2012;125(15):2688–2693.
9.
HarbHMGallosIDChuJHarbMCoomarasamyA. The effect of endometriosis on in vitro fertilisation outcome: a systematic review and meta-analysis. BJOG. 2013;120(11):1308–1320.
10.
BarbosaMAPTeixeiraDMNavarroPAFerrianiRANastriCOMartinsWP. The impact of endometriosis and its staging on assisted reproduction outcomes: a systematic review and meta-analysis. Ultrasound Obstet Gynecol. 2014;44(3):261–278.
11.
SimónCGutiérrezAVidalA. Outcome of patients with endometriosis in assisted reproduction: results from in-vitro fertilization and oocyte donation. Hum Reprod. 1994;9(4):725–729.
12.
DíazIDíazINavarroJ. Impact of stage iii–iv endometriosis on recipients of sibling oocytes: matched case-control study. Fertil Steril. 2000;74(1):31–34.
13.
BarcelosIDVieiraRCFerreiraEMMartinsWPFerrianiRANavarroPA. Comparative analysis of the spindle and chromosome configurations of in vitro–matured oocytes from patients with endometriosis and from control subjects: a pilot study. Fertil Steril. 2009;92(5):1749–1752.
14.
AssouSAnahoryTPantescoV. The human cumulus–oocyte complex gene-expression profile. Hum Reprod. 20062006;21(7):1705–1719.
15.
AssouSHaouziDMahmoudK. A non-invasive test for assessing embryo potential by gene expression profiles of human cumulus cells: a proof of concept study. Mol Hum Reprod. 20082008;14(12):711–719.
16.
AssouSHaouziDDe VosJHamamahS. Human cumulus cells as biomarkers for embryo and pregnancy outcomes. Mol Hum Reprod. 2010;16(8):531–538.
17.
GascaSPellestorFAssouS. Identifying new human oocyte marker genes: a microarray approach. Reprod Biomed Online. 2008;14(2):175–183.
18.
OuandaogoZGHaouziDAssouS. Human cumulus cells molecular signature in relation to oocyte nuclear maturity stage. PLoS One. 2011;6(11):e27179.
19.
OuandaogoZGFrydmanNHestersL. Differences in transcriptomic profiles of human cumulus cells isolated from oocytes at GV, MI and MII stages after in vivo and in vitro oocyte maturation. Human Reproduction. August 1, 20122012;27(8):2438–2447.
20.
HamelMDufortIRobertC. Identification of differentially expressed markers in human follicular cells associated with competent oocytes. Hum Reprod. 2008;23(5):1118–1127.
21.
HaouziDMahmoudKFourarM. Identification of new biomarkers of human endometrial receptivity in the natural cycle. Hum Reprod. 2009;24(1):198–205.
22.
CarvalhoLSamadderAAgarwalAFernandesLAbrãoM. Oxidative stress biomarkers in patients with endometriosis: systematic review. Arch Gynecol Obstet. 2012;286(4):1033–1040.
23.
AgarwalAAponte-MelladoAPremkumarBShamanAGuptaS. The effects of oxidative stress on female reproduction: a review. Reprod Biol Endocrinol. 2012;10(1):49.
24.
NavarroPALiuLKeefeDL. In vivo effects of arsenite on meiosis, preimplantation development, and apoptosis in the mouse. Biol Reprod. 2004;70(4):980–985.
25.
NavarroPALiuLFerrianiRAKeefeDL. Arsenite induces aberrations in meiosis that can be prevented by coadministration of N-acetylcysteine in mice. Fertil Steril. 2006;85(suppl 1):1187–1194.
26.
PrietoLQuesadaJFCamberoO. Analysis of follicular fluid and serum markers of oxidative stress in women with infertility related to endometriosis. Fertil Steril. 2012;98(1):126–130.
27.
LiuF HLLiuYShiYDuH. The expression and role of oxidative stress markers in the serum and follicular fluid of patients with endometriosis. Clin Exp Obstet Gynecol. 2013;40(3):372–376.
28.
SinghAKChattopadhyayRChakravartyBChaudhuryK. Markers of oxidative stress in follicular fluid of women with endometriosis and tubal infertility undergoing IVF. Reprod Toxicol. 2013;42(0):116–124.
ChadaSLe BeauMMCaseyLNewburgerPE. Isolation and chromosomal localization of the human glutathione peroxidase gene. Genomics. 1990;6(2):268–271.
31.
JanuelCEl HentatiF-ZCarrerasM. Phospholipid-hydroperoxide glutathione peroxidase (GPx-4) localization in resting platelets, and compartmental change during platelet activation. Biochim Biophys Acta. 2006;1761(10):1228–1234.
32.
RoveriACasascoAMaiorinoMDalanPCalligaroAUrsiniF. Phospholipid hydroperoxide glutathione peroxidase of rat testis. Gonadotropin dependence and immunocytochemical identification. J Biol Chem. 1992;267(9):6142–6146.
33.
MatzukMMDionneLGuoQKumarTRLebovitzRM. Ovarian function in superoxide dismutase 1 and 2 knockout mice. Endocrinology. 1998;139(9):4008–4011.
34.
SchneiderMFörsterHBoersmaA. Mitochondrial glutathione peroxidase 4 disruption causes male infertility. FASEB J. 2009;23(9):3233–3242.
35.
American Society for Reproductive M. Revised American Society for Reproductive Medicine classification of endometriosis: 1996. Fertil Steril. 1997;67(5):817–821.
36.
Alpha Scientists in Reproductive Medicine and ESHRE Special Interest Group of Embryology. The Istanbul consensus workshop on embryo assessment: proceedings of an expert meeting. Hum Reprod. 2011;26(6):1270–1283.
37.
SchmittgenTDZakrajsekBAMillsAGGornVSingerMJReedMW. Quantitative reverse transcription–polymerase chain reaction to study mRNA Decay: comparison of endpoint and real-time methods. Anal Biochem. 2000;285(2):194–204.
38.
LivakKJSchmittgenTD. Analysis of relative gene expression data using real-time quantitative PCR and the 2−ΔΔCT method. Methods. 2001;25(4):402–408.
39.
SAS INSTITUTE. SAS/STAT 2003: user’s guide: statistics version 9.1.3, (compact disc) [computer program]2003.
40.
CohenJ. Statistical Power Analysis for the Behavioral Sciences Lawrence Erlbaum Associates, Hillsdale, NJ 1988.
41.
OpøienHKFedorcsakPOmlandAK. In vitro fertilization is a successful treatment in endometriosis-associated infertility. Fertil Steril. 2012;97(4):912–918.
42.
MatosLStevensonDGomesFSilva-CarvalhoJLAlmeidaH. Superoxide dismutase expression in human cumulus oophorus cells. Mol Hum Reprod. 2009;15(7):411–419.
43.
BorcheltDRLeeMKSluntHS. Superoxide dismutase 1 with mutations linked to familial amyotrophic lateral sclerosis possesses significant activity. Proc Natl Acad Sci. 1994;91(17):8292–8296.
44.
FujiiJIuchiYOkadaF. Fundamental roles of reactive oxygen species and protective mechanisms in the female reproductive system. Reprod Biol Endocrinol. 2005;3(1):43.
45.
AgarwalASaidTMBedaiwyMABanerjeeJAlvarezJG. Oxidative stress in an assisted reproductive techniques setting. Fertil Steril. 2006;86(3):503–512.
46.
El MouatassimSGuérinPMénézoY. Expression of genes encoding antioxidant enzymes in human and mouse oocytes during the final stages of maturation. Mol Hum Reprod. 1999;5(8):720–725.
47.
AgarwalAGuptaSSharmaR. Role of oxidative stress in female reproduction. Reprod Biol Endocrinol. 2005;3(1):28.
48.
TatemotoHSakuraiNMutoN. Protection of porcine oocytes against apoptotic cell death caused by oxidative stress during in vitro maturation: role of cumulus cells. Biol Reprod. 20002000;63(3):805–810.
49.
SuzukiTSuginoNFukayaT. Superoxide dismutase in normal cycling human ovaries: immunohistochemical localization and characterization. Fertil Steril. 1999;72(4):720–726.
50.
WardlePGMcLaughlinEAMcDermottAMitchellJDRayBDHullMGR. Endometriosis and ovulatory disorder: reduced fertilisation in vitro compared with tubal and unexplained infertility. Lancet. 1985;326(8449):236–239.
51.
HarlowCRCahillDJMaileLA. Reduced preovulatory granulosa cell steroidogenesis in women with endometriosis. J Clin Endocrinol Metab. 1996;81(1):426–429.
52.
GomesFMNavarroPAde AbreuLGFerrianiRAdos ReisRMde MouraMD. Effect of peritoneal fluid from patients with minimal/mild endometriosis on progesterone release by human granulosa-lutein cells obtained from infertile patients without endometriosis: a pilot study. Eur J Obstet Gynecol Reprod Biol. 2008;138(1):60–65.
53.
LaPoltPSHongLS. Inhibitory effects of superoxide dismutase and cyclic guanosine 3’,5’-monophosphate on estrogen production in cultured rat granulosa cells. Endocrinology. 1995;136(12):5533–5539.
54.
VeritFFErelOKocyigitA. Association of increased total antioxidant capacity and anovulation in nonobese infertile patients with clomiphene citrate–resistant polycystic ovary syndrome. Fertil Steril. 2007;88(2):418–424.
