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

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This study found higher follicular fluid concentrations of 8-hydroxy-2′-deoxyguanosine and vitamin E in infertile women with endometriosis compared to controls.

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This study compared eight oxidative stress markers measured in serum and follicular fluid of infertile women with endometriosis versus infertile controls undergoing controlled ovarian stimulation for intracytoplasmic sperm injection, analyzing samples collected at oocyte retrieval from 29 endometriosis cases and 32 controls (plus 43 and 44 serum samples). The endometriosis group had higher serum glutathione and superoxide dismutase, lower serum total antioxidant capacity, and—within the follicular microenvironment—higher 8-hydroxy-2′-deoxyguanosine (8OHdG) and vitamin E, indicating both systemic and follicular oxidative stress with oxidative DNA damage. A key limitation acknowledged by the authors is that causality cannot be established from these observational biomarker comparisons. This paper is centrally about endometriosis — it reports increased 8OHdG in follicular fluid as evidence of oxidative DNA damage associated with endometriosis-related infertility.

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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.
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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. Similar content being viewed by others

References

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Kidney Int 49:1304–1313 Acknowledgments The authors are grateful to the staff of the Human Reproduction Division, Department of Obstetrics and Gynecology, Ribeirao Preto School of Medicine, University of Sao Paulo (FMRP-USP), especially Maria Cristina Picinato and Roberta Cristina Giorgenon for FF collection, to the Nutrition and Metabolism Laboratory, FMRP-USP, especially Paula Payão and Virginia Lipoli for technical support to Jhenifer Kliemchen Rodrigues for assisting with the quantification of OS markers and to Suleimy Cristina Mazin for the statistical advice. Author information Authors and Affiliations Corresponding author Additional information This study received financial support from the National Council for Scientific and Technological Development (CNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico; 474858/2009-0; 309056/2009-8; 503867/2010-1) and the Sao Paulo Research Foundation (FAPESP – Fundação de Amparo à Pesquisa do Estado de São Paulo; 2008/58197-6; 2008/56373-1; 2014/15866-6). Rights and permissions About this article Cite this article Da Broi, M.G., de Albuquerque, F.O., de Andrade, A.Z. et al. Increased concentration of 8-hydroxy-2′-deoxyguanosine in follicular fluid of infertile women with endometriosis. Cell Tissue Res 366, 231–242 (2016). https://doi.org/10.1007/s00441-016-2428-4 Received: Accepted: Published: Issue date: DOI: https://doi.org/10.1007/s00441-016-2428-4

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endometriosis

MeSH descriptors

Deoxyguanosine Endometriosis Follicular Fluid Infertility, Female 8-Hydroxy-2'-Deoxyguanosine Adult Biomarkers Biomarkers Case-Control Studies Deoxyguanosine Deoxyguanosine Endometriosis Endometriosis Endometriosis Female Follicular Fluid Humans Infertility, Female Infertility, Female Infertility, Female

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