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Published in: Reproductive Biology and Endocrinology 1/2016

Open Access 01-12-2016 | Research

Antioxidants reduce oxidative stress in follicular fluid of aged women undergoing IVF

Authors: Alice Luddi, Angela Capaldo, Riccardo Focarelli, Martina Gori, Giuseppe Morgante, Paola Piomboni, Vincenzo De Leo

Published in: Reproductive Biology and Endocrinology | Issue 1/2016

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Abstract

Background

The status characterized by the imbalance between pro-oxidants and antioxidants molecules, defined as oxidative stress, has been suggested to be involved in the pathogenesis of subfertility in females. This study aims to evaluate the impact of a complete micronutrients supplementation on oxidative stress levels in follicular microenvironment as well as on in vitro fertilization (IVF) outcome.

Methods

This preliminary study was conducted between January 2014 and July 2015 at the Siena University Hospital Infertility Clinic. Serum and follicular fluid were collected from infertile women aged > 39 years who underwent two in vitro fertilization cycles: in the first cycle they were treated with GnRH-antagonist protocol and gonadotropins for controlled ovarian hyperstimulation, whereas in the second cycle ovarian stimulation protocol was associated to micronutrients supplementation, starting three months earlier. Protein oxidation levels and total antioxidant capacity in serum and in follicular fluid were evaluated in IVF cycles with or without micronutrients supplementation. Differences in IVF outcome parameters were statistically evaluated.

Results

Two-dimensional electrophoresis analyses demonstrated that when patients assumed micronutrients before IVF cycles, follicular fluid and serum proteins were protected from oxidative damage. Comparable results were obtained when total antioxidant capacity was measured. Moreover, the mean number of good quality oocytes retrieved when patients received micronutrients supplementation was significantly increased.

Conclusion

The additional treatment with micronutrients, starting three months before IVF cycles, protects the follicular microenvironment from oxidative stress, thus increasing the number of good quality oocytes recovered at the pick up.
Literature
2.
go back to reference Agarwal A, Aponte-Mellado A, Premkumar BJ, et al. The effects of oxidative stress on female reproduction: a review. Reprod Biol Endocrinol. 2012;10:49.CrossRefPubMedPubMedCentral Agarwal A, Aponte-Mellado A, Premkumar BJ, et al. The effects of oxidative stress on female reproduction: a review. Reprod Biol Endocrinol. 2012;10:49.CrossRefPubMedPubMedCentral
5.
go back to reference Swamy M, Sirajudeen KNS, Chandran G. Nitric oxide (NO), citrulline-NO cycle enzymes, glutamine synthetase, and oxidative status in kainic acid-mediated excitotoxicity in rat brain. Drug Chem Toxicol. 2009;32:326–31.CrossRefPubMed Swamy M, Sirajudeen KNS, Chandran G. Nitric oxide (NO), citrulline-NO cycle enzymes, glutamine synthetase, and oxidative status in kainic acid-mediated excitotoxicity in rat brain. Drug Chem Toxicol. 2009;32:326–31.CrossRefPubMed
6.
go back to reference Uttara B, Singh AV, Zamboni P, Mahajan RT. Oxidative stress and neurodegenerative diseases: a review of upstream and downstream antioxidant therapeutic options. Curr Neuropharmacol. 2009;7:65–74.CrossRefPubMedPubMedCentral Uttara B, Singh AV, Zamboni P, Mahajan RT. Oxidative stress and neurodegenerative diseases: a review of upstream and downstream antioxidant therapeutic options. Curr Neuropharmacol. 2009;7:65–74.CrossRefPubMedPubMedCentral
7.
go back to reference Duan J, Kasper DL. Oxidative depolymerization of polysaccharides by reactive oxygen/nitrogen species. Glycobiology. 2011;21:401–9.CrossRefPubMed Duan J, Kasper DL. Oxidative depolymerization of polysaccharides by reactive oxygen/nitrogen species. Glycobiology. 2011;21:401–9.CrossRefPubMed
9.
go back to reference Davies MJ, Donkor R, Dunster CA, Gee CA, Jonas S, Willson RL. Desferrioxamine (Desferal) and superoxide free radicals. Formation of an enzyme-damaging nitroxide. Biochem J. 1987;246:725–9.CrossRefPubMedPubMedCentral Davies MJ, Donkor R, Dunster CA, Gee CA, Jonas S, Willson RL. Desferrioxamine (Desferal) and superoxide free radicals. Formation of an enzyme-damaging nitroxide. Biochem J. 1987;246:725–9.CrossRefPubMedPubMedCentral
11.
go back to reference Höhn A, Jung T, Grune T. Pathophysiological importance of aggregated damaged proteins. Free Radic Biol Med. 2014;71:70–89.CrossRefPubMed Höhn A, Jung T, Grune T. Pathophysiological importance of aggregated damaged proteins. Free Radic Biol Med. 2014;71:70–89.CrossRefPubMed
12.
go back to reference Salo DC, Pacifici RE, Lin SW, Giulivi C, Davies KJ. Superoxide dismutase undergoes proteolysis and fragmentation following oxidative modification and inactivation. J Biol Chem. 1990;265:11919–27.PubMed Salo DC, Pacifici RE, Lin SW, Giulivi C, Davies KJ. Superoxide dismutase undergoes proteolysis and fragmentation following oxidative modification and inactivation. J Biol Chem. 1990;265:11919–27.PubMed
13.
go back to reference Berlett BS, Stadtman ER. Protein oxidation in aging, disease, and oxidative stress. J Biol Chem. 1997;272:20313–6.CrossRefPubMed Berlett BS, Stadtman ER. Protein oxidation in aging, disease, and oxidative stress. J Biol Chem. 1997;272:20313–6.CrossRefPubMed
14.
go back to reference Sugino N, Shimamura K, Takiguchi S, Tamura H, Ono M, Nakata M, Nakamura Y, Ogino K, Uda T, Kato H. Changes in activity of superoxide dismutase in the human endometrium throughout the menstrual cycle and in early pregnancy. Hum Reprod. 1996;11:1073–8.CrossRefPubMed Sugino N, Shimamura K, Takiguchi S, Tamura H, Ono M, Nakata M, Nakamura Y, Ogino K, Uda T, Kato H. Changes in activity of superoxide dismutase in the human endometrium throughout the menstrual cycle and in early pregnancy. Hum Reprod. 1996;11:1073–8.CrossRefPubMed
15.
go back to reference Aitken RJ. The Amoroso Lecture. The human spermatozoon--a cell in crisis? J Reprod Fertil. 1999;115:1–7.CrossRefPubMed Aitken RJ. The Amoroso Lecture. The human spermatozoon--a cell in crisis? J Reprod Fertil. 1999;115:1–7.CrossRefPubMed
16.
go back to reference Oyawoye O, Abdel Gadir A, Garner A, Constantinovici N, Perrett C, Hardiman P. Antioxidants and reactive oxygen species in follicular fluid of women undergoing IVF: relationship to outcome. Hum Reprod. 2003;18:2270–4.CrossRefPubMed Oyawoye O, Abdel Gadir A, Garner A, Constantinovici N, Perrett C, Hardiman P. Antioxidants and reactive oxygen species in follicular fluid of women undergoing IVF: relationship to outcome. Hum Reprod. 2003;18:2270–4.CrossRefPubMed
17.
go back to reference Pasqualotto EB, Agarwal A, Sharma RK, Izzo VM, Pinotti JA, Joshi NJ, Rose BI. Effect of oxidative stress in follicular fluid on the outcome of assisted reproductive procedures. Fertil Steril. 2004;81:973–6.CrossRefPubMed Pasqualotto EB, Agarwal A, Sharma RK, Izzo VM, Pinotti JA, Joshi NJ, Rose BI. Effect of oxidative stress in follicular fluid on the outcome of assisted reproductive procedures. Fertil Steril. 2004;81:973–6.CrossRefPubMed
18.
go back to reference Appasamy M, Jauniaux E, Serhal P, Al-Qahtani A, Groome NP, Muttukrishna S. Evaluation of the relationship between follicular fluid oxidative stress, ovarian hormones, and response to gonadotropin stimulation. Fertil Steril. 2008;89:912–21.CrossRefPubMed Appasamy M, Jauniaux E, Serhal P, Al-Qahtani A, Groome NP, Muttukrishna S. Evaluation of the relationship between follicular fluid oxidative stress, ovarian hormones, and response to gonadotropin stimulation. Fertil Steril. 2008;89:912–21.CrossRefPubMed
19.
go back to reference Fujimoto VY, Bloom MS, Huddleston HG, Shelley WB, Ocque AJ, Browne RW. Correlations of follicular fluid oxidative stress biomarkers and enzyme activities with embryo morphology parameters during in vitro fertilization. Fertil Steril. 2011;96:1357–61.CrossRefPubMed Fujimoto VY, Bloom MS, Huddleston HG, Shelley WB, Ocque AJ, Browne RW. Correlations of follicular fluid oxidative stress biomarkers and enzyme activities with embryo morphology parameters during in vitro fertilization. Fertil Steril. 2011;96:1357–61.CrossRefPubMed
20.
go back to reference Pereira AC, Martel F. Oxidative stress in pregnancy and fertility pathologies. Cell Biol Toxicol. 2014;30:301–12.CrossRefPubMed Pereira AC, Martel F. Oxidative stress in pregnancy and fertility pathologies. Cell Biol Toxicol. 2014;30:301–12.CrossRefPubMed
21.
go back to reference Bedaiwy MA, Elnashar SA, Goldberg JM, Sharma R, Mascha EJ, Arrigain S, Agarwal A, Falcone T. Effect of follicular fluid oxidative stress parameters on intracytoplasmic sperm injection outcome. Gynecol Endocrinol. 2012;28:51–5.CrossRefPubMed Bedaiwy MA, Elnashar SA, Goldberg JM, Sharma R, Mascha EJ, Arrigain S, Agarwal A, Falcone T. Effect of follicular fluid oxidative stress parameters on intracytoplasmic sperm injection outcome. Gynecol Endocrinol. 2012;28:51–5.CrossRefPubMed
22.
go back to reference Palini S, Benedetti S, Tagliamonte MC, De Stefani S, Primiterra M, Polli V, Rocchi P, Catalani S, Battistelli S, Canestrari F, Bulletti C. Influence of ovarian stimulation for IVF/ICSI on the antioxidant defence system and relationship to outcome. Reprod Biomed Online. 2014;29:65–71.CrossRefPubMed Palini S, Benedetti S, Tagliamonte MC, De Stefani S, Primiterra M, Polli V, Rocchi P, Catalani S, Battistelli S, Canestrari F, Bulletti C. Influence of ovarian stimulation for IVF/ICSI on the antioxidant defence system and relationship to outcome. Reprod Biomed Online. 2014;29:65–71.CrossRefPubMed
23.
24.
go back to reference Noctor G, Lelarge-Trouverie C, Mhamdi A. The metabolomics of oxidative stress. Phytochemistry. 2014;112:33–53.CrossRefPubMed Noctor G, Lelarge-Trouverie C, Mhamdi A. The metabolomics of oxidative stress. Phytochemistry. 2014;112:33–53.CrossRefPubMed
25.
go back to reference Al-Azemi MK, Omu AE, Fatinikun T, Mannazhath N, Abraham S. Factors contributing to gender differences in serum retinol and alpha-tocopherol in infertile couples. Reprod Biomed Online. 2009;19:583–90.CrossRefPubMed Al-Azemi MK, Omu AE, Fatinikun T, Mannazhath N, Abraham S. Factors contributing to gender differences in serum retinol and alpha-tocopherol in infertile couples. Reprod Biomed Online. 2009;19:583–90.CrossRefPubMed
26.
go back to reference Szymański W, Kazdepka-Ziemińska A. Effect of homocysteine concentration in follicular fluid on a degree of oocyte maturity. Ginekol Pol. 2003;74:1392–6.PubMed Szymański W, Kazdepka-Ziemińska A. Effect of homocysteine concentration in follicular fluid on a degree of oocyte maturity. Ginekol Pol. 2003;74:1392–6.PubMed
27.
go back to reference Ebner T, Moser M, Sommergruber M, Tews G. Selection based on morphological assessment of oocytes and embryos at different stages of preimplantation development: a review. Hum Reprod Update. 2003;9:251–62. Ebner T, Moser M, Sommergruber M, Tews G. Selection based on morphological assessment of oocytes and embryos at different stages of preimplantation development: a review. Hum Reprod Update. 2003;9:251–62.
29.
go back to reference de Lamirande E, Gagnon C. Paradoxical effect of reagents for sulfhydryl and disulfide groups on human sperm capacitation and superoxide production. Free Radic Biol Med. 1998;25:803–17.CrossRefPubMed de Lamirande E, Gagnon C. Paradoxical effect of reagents for sulfhydryl and disulfide groups on human sperm capacitation and superoxide production. Free Radic Biol Med. 1998;25:803–17.CrossRefPubMed
30.
go back to reference Görg A, Postel W, Günther S. The current state of two-dimensional electrophoresis with immobilized pH gradients. Electrophoresis. 1988;9:531–46.CrossRefPubMed Görg A, Postel W, Günther S. The current state of two-dimensional electrophoresis with immobilized pH gradients. Electrophoresis. 1988;9:531–46.CrossRefPubMed
31.
go back to reference Bjellqvist B, Pasquali C, Ravier F, Sanchez JC, Hochstrasser D. A nonlinear wide-range immobilized pH gradient for two-dimensional electrophoresis and its definition in a relevant pH scale. Electrophoresis. 1993;14:1357–65.CrossRefPubMed Bjellqvist B, Pasquali C, Ravier F, Sanchez JC, Hochstrasser D. A nonlinear wide-range immobilized pH gradient for two-dimensional electrophoresis and its definition in a relevant pH scale. Electrophoresis. 1993;14:1357–65.CrossRefPubMed
32.
go back to reference Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970;227:680–5.CrossRefPubMed Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970;227:680–5.CrossRefPubMed
33.
go back to reference Towbin H, Staehelin T, Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci U S A. 1979;76:4350–4.CrossRefPubMedPubMedCentral Towbin H, Staehelin T, Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci U S A. 1979;76:4350–4.CrossRefPubMedPubMedCentral
34.
go back to reference Joshi R, Adhikari S, Patro BS, Chattopadhyay S, Mukherjee T. Free radical scavenging behavior of folic acid: evidence for possible antioxidant activity. Free Radic Biol Med. 2001;30:1390–9.CrossRefPubMed Joshi R, Adhikari S, Patro BS, Chattopadhyay S, Mukherjee T. Free radical scavenging behavior of folic acid: evidence for possible antioxidant activity. Free Radic Biol Med. 2001;30:1390–9.CrossRefPubMed
35.
go back to reference Ebisch IMW, Thomas CMG, Peters WHM, Braat DD, Steegers-Theunissen RP. The importance of folate, zinc and antioxidants in the pathogenesis and prevention of subfertility. Hum Reprod Update. 2007;13:163–74.CrossRefPubMed Ebisch IMW, Thomas CMG, Peters WHM, Braat DD, Steegers-Theunissen RP. The importance of folate, zinc and antioxidants in the pathogenesis and prevention of subfertility. Hum Reprod Update. 2007;13:163–74.CrossRefPubMed
36.
go back to reference Eaton S. The biochemical basis of antioxidant therapy in critical illness. Proc Nutr Soc. 2006;65:242–9.CrossRefPubMed Eaton S. The biochemical basis of antioxidant therapy in critical illness. Proc Nutr Soc. 2006;65:242–9.CrossRefPubMed
37.
go back to reference Piomboni P, Stendardi A, Gambera L, Tatone C, Coppola L, De Leo V, Focarelli R. Protein modification as oxidative stress marker in normal and pathological human seminal plasma. Redox Rep. 2012;17:227–32.CrossRefPubMed Piomboni P, Stendardi A, Gambera L, Tatone C, Coppola L, De Leo V, Focarelli R. Protein modification as oxidative stress marker in normal and pathological human seminal plasma. Redox Rep. 2012;17:227–32.CrossRefPubMed
38.
go back to reference Forges T, Monnier-Barbarino P, Alberto JM, Guéant-Rodriguez RM, Daval JL, Guéant JL. Impact of folate and homocysteine metabolism on human reproductive health. Hum Reprod Update. 2007;13:225–38.CrossRefPubMed Forges T, Monnier-Barbarino P, Alberto JM, Guéant-Rodriguez RM, Daval JL, Guéant JL. Impact of folate and homocysteine metabolism on human reproductive health. Hum Reprod Update. 2007;13:225–38.CrossRefPubMed
39.
go back to reference Bray TM, Bettger WJ. The physiological role of zinc as an antioxidant. Free Radic Biol Med. 1990;8:281–91.CrossRefPubMed Bray TM, Bettger WJ. The physiological role of zinc as an antioxidant. Free Radic Biol Med. 1990;8:281–91.CrossRefPubMed
40.
go back to reference Tamura H, Takasaki A, Miwa I, Taniguchi K, Maekawa R, Asada H, Taketani T, Matsuoka A, Yamagata Y, Shimamura K, Morioka H, Ishikawa H, Reiter RJ, Sugino N. Oxidative stress impairs oocyte quality and melatonin protects oocytes from free radical damage and improves fertilization rate. J Pineal Res. 2008;44:280–7.CrossRefPubMed Tamura H, Takasaki A, Miwa I, Taniguchi K, Maekawa R, Asada H, Taketani T, Matsuoka A, Yamagata Y, Shimamura K, Morioka H, Ishikawa H, Reiter RJ, Sugino N. Oxidative stress impairs oocyte quality and melatonin protects oocytes from free radical damage and improves fertilization rate. J Pineal Res. 2008;44:280–7.CrossRefPubMed
41.
go back to reference Chavarro JE, Rich-Edwards JW, Rosner BA, Willett WC. Iron intake and risk of ovulatory infertility. Obstet Gynecol. 2006;108:1145–52.CrossRefPubMed Chavarro JE, Rich-Edwards JW, Rosner BA, Willett WC. Iron intake and risk of ovulatory infertility. Obstet Gynecol. 2006;108:1145–52.CrossRefPubMed
42.
go back to reference Takahashi T, Takahashi E, Igarashi H, Tezuka N, Kurachi H. Impact of oxidative stress in aged mouse oocytes on calcium oscillations at fertilization. Mol Reprod Dev. 2003;66:143–52.CrossRefPubMed Takahashi T, Takahashi E, Igarashi H, Tezuka N, Kurachi H. Impact of oxidative stress in aged mouse oocytes on calcium oscillations at fertilization. Mol Reprod Dev. 2003;66:143–52.CrossRefPubMed
43.
go back to reference Lerchbaum E, Obermayer-Pietsch B. Vitamin D and fertility: a systematic review. Eur J Endocrinol. 2012;166:765–78.CrossRefPubMed Lerchbaum E, Obermayer-Pietsch B. Vitamin D and fertility: a systematic review. Eur J Endocrinol. 2012;166:765–78.CrossRefPubMed
44.
go back to reference Bianchi L, Gagliardi A, Landi C, Focarelli R, De Leo V, Luddi A, Bini L, Piomboni P. Protein pathways working in human follicular fluid: the future for tailored IVF? Exp Rev Mol Med 2016, in press. Bianchi L, Gagliardi A, Landi C, Focarelli R, De Leo V, Luddi A, Bini L, Piomboni P. Protein pathways working in human follicular fluid: the future for tailored IVF? Exp Rev Mol Med 2016, in press.
45.
go back to reference Irani M, Minkoff H, Seifer DB, Merhi Z. Vitamin D increases serum levels of the soluble receptor for advanced glycation End products in women with PCOS. J Clin Endocrinol Metab. 2014;99:E886–90.CrossRefPubMed Irani M, Minkoff H, Seifer DB, Merhi Z. Vitamin D increases serum levels of the soluble receptor for advanced glycation End products in women with PCOS. J Clin Endocrinol Metab. 2014;99:E886–90.CrossRefPubMed
46.
go back to reference Fujii EY, Nakayama M. The measurements of RAGE, VEGF, and AGEs in the plasma and follicular fluid of reproductive women: the influence of aging. Fert Steril. 2010;94:694–700.CrossRef Fujii EY, Nakayama M. The measurements of RAGE, VEGF, and AGEs in the plasma and follicular fluid of reproductive women: the influence of aging. Fert Steril. 2010;94:694–700.CrossRef
47.
go back to reference Bonetti TC, Borges Jr E, Braga DP, Iaconelli Jr A, Kleine JP, Silva ID. Intrafollicular soluble receptor for advanced glycation end products (sRAGE) and embryo quality in assisted reproduction. Reprod Biomed Online. 2013;26:62–7.CrossRefPubMed Bonetti TC, Borges Jr E, Braga DP, Iaconelli Jr A, Kleine JP, Silva ID. Intrafollicular soluble receptor for advanced glycation end products (sRAGE) and embryo quality in assisted reproduction. Reprod Biomed Online. 2013;26:62–7.CrossRefPubMed
48.
go back to reference Tatone C, Amicarelli F, Carbone MC, Monteleone P, Caserta D, Marci R, Artini PG, Piomboni P, Focarelli R. Cellular and molecular aspects of ovarian follicle ageing. Hum Reprod Update. 2008;14:131–42.CrossRefPubMed Tatone C, Amicarelli F, Carbone MC, Monteleone P, Caserta D, Marci R, Artini PG, Piomboni P, Focarelli R. Cellular and molecular aspects of ovarian follicle ageing. Hum Reprod Update. 2008;14:131–42.CrossRefPubMed
Metadata
Title
Antioxidants reduce oxidative stress in follicular fluid of aged women undergoing IVF
Authors
Alice Luddi
Angela Capaldo
Riccardo Focarelli
Martina Gori
Giuseppe Morgante
Paola Piomboni
Vincenzo De Leo
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Reproductive Biology and Endocrinology / Issue 1/2016
Electronic ISSN: 1477-7827
DOI
https://doi.org/10.1186/s12958-016-0184-7

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