Austin J In Vitro Fertili. 2015;2(1): 1011.
Institute of Research and Technology in Animal Reproduction, University of Buenos Aires, Argentina
*Corresponding author: Sergio Morado, Institute of Research and Technology in Animal Reproduction, Area of Biochemistry, School of Veterinary Science, University of Buenos Aires
Received: November 08, 2014; Accepted: November 09, 2014; Published: February 09, 2015
The role of Reactive Oxygen Species (ROS) and redox state in reproductive processes is still controversial. The presence of antioxidant enzymes in several mammalian species suggests that defense mechanisms are conserved and would be important for the last stages of oocyte maturation and for early embryo development . However, in some species, as in the bovine, the addition of antioxidants to the culture medium resulted in a decrease in the percentage of blastocysts produced in vitro . Moreover, in sperm, ROS have been described to have an important participation in the regulation of all the functional parameters, including motility, capacitation, sperm-zona pellucida interaction, acrosome reaction and sperm-oocyte fusion [3,4].
Several studies propose that physiological ranges of ROS concentration in the follicular fluid may be the result of the balance between pro-oxidant systems and scavengers and would be necessary for normal oocyte development . Therefore, certain ROS levels could be indicators of healthy oocytes, while their excess would indicate oxidative stress, which could compromise In Vitro Fertilization (IVF) [5-8]. The total antioxidant capacity of the follicular fluid is considered a predictive marker for a successful IVF . The beneficial effect of the follicular fluid against oxidative damage would be due in part to a high Superoxide Dismutase (SOD) activity, which has been shown to have a positive correlation with an increase in cytoplasm maturation in the porcine oocyte . In contrast, in humans, a high SOD activity has been associated with oocytes which failed to be fertilized , but physiological concentrations of another antioxidant enzyme, glutathione peroxidase, presented a positive correlation with IVF rates .
In addition, the antioxidant deposits (as mRNA or proteins) in the oocyte during its growth and maturation would also be important for embryos to obtain developmental competence . In somatic cells, the presence of a mechanism of regulation of the synthesis of antioxidants in pre and post translation stages has been proved [12-14]. This could be relevant for oocytes during the maturation process, in which translation and post-translation regulation of protein synthesis prevail [15-17]. In the mouse, mRNA which codify for glutathione peroxidase, SOD and γ-glutamylcysteine synthetase (important enzyme for glutathione synthesis) both in immature and mature oocytes was detected, while in humans the regulation of glutathione peroxidase and SOD transcripts has been documented . As regards catalase, mRNA has been found in fertilized oocytes in the mouse and bovine , but not in humans . Catalase activity has also been detected in immature and in vitro matured bovine oocytes .
It has been shown that several transcription factors involved in developmental processes are regulated by the intracellular red ox potential [21-26]. These factors are sensitive to oxidation or S-glutathionylation by ROS and require NAD (P) H o NAD (P)+ . In somatic cells, it has been observed that red ox state and ROS levels are negatively related. A high intracellular oxidative activity (for example, due to the increase in the mitochondrial oxygen consumption rate) is usually associated with a decrease in ROS production . In the mouse, it has been demonstrated that redox state and ROS production regulation have a fundamental importance in early embryo development .
In the bovine, we found clear and distinctive metabolic patterns as regards redox activity and fluctuations in ROS production between non-activated oocytes, in vitro fertilized and parthenogenetically activated oocytes; sperm-activated oocytes presented an increase in oxidative activity corresponding with the initiation of pronuclear formation and first mitotic division, suggesting increased demands of energy for these events . This increase can be related with results obtained by other groups who described that one and two cell bovine embryos are dependent on mitochondrial oxidative phosphorylation for energy supply, consuming oxidative substrates to produce ATP [30,31]. Coincidently, a higher oxygen consumption rate was detected prior to cleavage in bovine zygotes . It remains to be studied if these metabolic patterns are shared by other species, including humans.
In conclusion, there is still much to investigate about the participation of ROS and the influence of red ox state in oocyte maturation, IVF and embryo development. The study of the characteristic behaviors in red ox activity and ROS level fluctuations during early development could be integrated in our understanding of indicators of oocyte quality and embryo developmental competence. Therefore, future works should be carried out to clarify the role of these metabolic parameters in order to improve IVF and other assisted reproduction techniques.
- Combelles CM, Gupta S, Agarwal A. Could oxidative stress influence the in-vitro maturation of oocytes? Reprod Biomed Online. 2009; 18: 864-880.
- Dalvit GC, Llanes SP, Descalzo A, Insani M, Beconi M, Cetica P. Effect of alpha-tocopherol and ascorbic acid on bovine oocyte in vitro maturation. Reproduction in Domestic Animals. 2005; 40: 93-97.
- Baker MA, Aitken RJ. The importance of redox regulated pathways in sperm cell biology. Mol Cell Endocrinol. 2004; 216: 47-54.
- Rivlin J, Mendel J, Rubinstein S, Etkovitz N, Breitbart H. Role of hydrogen peroxide in sperm capacitation and acrosome reaction. Biol Reprod. 2004; 70: 518-522.
- Attaran M, Pasqualotto E, Falcone T, Goldberg JM, Miller KF, Agarwal A, et al. The effect of follicular fluid reactive oxygen species on the outcome of in vitro fertilization. International Journal of Fertility and Women's Medicine. 2000; 45: 314-320.
- Agarwal A, Saleh RA, Bedaiwy MA. Role of reactive oxygen species in the pathophysiology of human reproduction. Fertil Steril. 2003; 79: 829-843.
- Pasqualotto EB, Agarwal A, Sharma RK, Izzo VM, Pinotti JA, Joshi NJ, et al. Effect of oxidative stress in follicular fluid on the outcome of assisted reproductive procedures. Fertil Steril. 2004; 81: 973-976.
- Wiener-Megnazi Z, Vardi L, Lissak A, Shnizer S, Reznik AZ, Ishai D, et al. Oxidative stress indices in follicular fluid as measured by the thermochemiluminescence assay correlate with outcome parameters in in-vitro fertilization. Fertility and Sterility. 2004; 82: 1171-1176.
- Tatemoto H, Ootaki K, Shigeta K, Muto N. Enhancement of developmental competence after in vitro fertilization of porcine oocytes after treatment with ascorbic acid 2-o- a glucoside during in vitro maturation. Biology of Reproduction. 2001; 65: 1800-1806.
- Sabatini L, Wilson C, Lower A, Al-Shawaf T, Grudzinskas JG. Superoxide dismutase activity in human follicular fluid after controlled ovarian hyperstimulation in women undergoing in-vitro fertilization. Fertility and Sterility. 1999; 72: 1027-1034.
- Paszkowski T, Traub AI, Robinson SY, McMaster D. Selenium dependent glutathione peroxidase activity in human follicular fluid. Clin Chim Acta. 1995; 236: 173-180.
- Forsberg H, Borg LA, Cagliero E, Eriksson UJ. Altered levels of scavenging enzymes in embryos subjected to a diabetic environment. Free Radic Res. 1996; 24: 451-459.
- Brown NM, Torres AS, Doan PE, O'Halloran TV. Oxygen and the copper chaperone CCS regulate posttranslational activation of Cu, Zn superoxide dismutase. Proceedings of the National Academy of Science of the United States of America. 2004; 101: 5518-5523.
- Rhee SG, Yang KS, Kang SW, Woo HA, Chang TS. Controlled elimination of intracellular H(2)O(2): regulation of peroxiredoxin, catalase, and glutathione peroxidase via post-translational modification. Antioxidants and Redox Signaling. 2005; 7: 619-626.
- Oh B, Hwang S, McLaughlin J, Solter D, Knowles BB. Timely translation during the mouse oocyte-to-embryo transition. Development. 2000; 127: 3795-3803.
- Eichenlaub-Ritter U, Vogt E, Yin H, Gosden R. Spindles, mitochondria and redox potential in ageing oocytes. Reprod Biomed Online. 2004; 8: 45-58.
- De La Fuente R. Chromatin modifications in the germinal vesicle (GV) of mammalian oocytes. Dev Biol. 2006; 292: 1-12.
- El Mouatassim S, Guerin P, Ménézo Y. Expression of genes encoding antioxidant enzymes in human and mouse oocytes during the final stages of maturation. Molecular Human Reproduction. 1999; 5: 720-725.
- Harvey MB, Arcellana-Panlilio MY, Zhang X, Schultz GA, Watsonet AJ. Expression of genes encoding antioxidant enzymes in preimplantation mouse and cow embryos and primary bovine oviduct cultures employed for embryo coculture. Biology of Reproduction. 1995; 53: 532-540.
- Cetica PD, Pintos LN, Dalvit GC, Beconi MT. Antioxidant enzyme activity and oxidative stress in bovine oocyte in vitro maturation. IUBMB Life. 2001; 51: 57-64.
- Dickinson DA, Forman HJ. Glutathione in defense and signaling: lessons from a small thiol. Ann N Y Acad Sci. 2002; 973: 488-504.
- Funato Y, Michiue T, Asashima M, Miki H. The thioredoxin-related redox-regulating protein nucleoredoxin inhibits Wnt-beta-catenin signalling through dishevelled. Nat Cell Biol. 2006; 8: 501-508.
- Imai S, Johnson FB, Marciniak RA, McVey M, Park PU, Guarente L. Sir2: an NAD-dependent histone deacetylase that connects chromatin silencing, metabolism, and aging. Cold Spring Harb Symp Quant Biol. 2000; 65: 297-302.
- Liu H, Colavitti R, Rovira II, Finkel T. Redox-dependent transcriptional regulation. Circ Res. 2005; 97: 967-974.
- Rahman I, Marwick J, Kirkham P. Redox modulation of chromatin remodeling: impact on histone acetylation and deacetylation, NF-kappaB and pro-inflammatory gene expression. Biochem Pharmacol. 2004; 68: 1255-1267.
- Zhang Q, Piston DW, Goodman RH. Regulation of corepressor function by nuclear NADH. Science. 2002; 295: 1895-1897.
- Dumollard R, Ward Z, Carroll J, Duchen MR. Regulation of redox metabolism in the mouse oocyte and embryo. Development. 2007; 134: 455-465.
- Boveris A, Cadenas E. Production of superoxide radicals and hydrogen peroxide in mitochondria. In Superoxide dismutase, Ed LW Oberley. Boca Raton: CRC Press. 1982; 15-30.
- Morado S, Cetica P, Beconi M, Thompson JG, Dalvit G. Reactive oxygen species production and redox state in parthenogenetic and sperm-mediated bovine oocyte activation. Reproduction. 2013; 145: 471-478.
- Kim JH, Niwa K, Lim JM, Okuda K. Effects of phosphate, energy substrates, and amino acids on development of in vitro-matured, in vitro-fertilized bovine oocytes in a chemically defined, protein-free culture medium. Biology of Reproduction. 1993; 48: 1320-1325.
- Thompson JG, Partridge RJ, Houghton FD, Cox CI, Leese HJ. Oxygen uptake and carbohydrate metabolism by in vitro derived bovine embryos. J Reprod Fertil. 1996; 106: 299-306.
- Lopes AS, Lane M, Thompson JG. Oxygen consumption and ROS production are increased at the time of fertilization and cell cleavage in bovine zygotes. Hum Reprod. 2010; 25: 2762-2773.