Oxidative Stress and Male Infertility: The Protective Role of Antioxidants
Abstract
:1. Introduction
2. Oxidative Stress and Male Infertility
2.1. Dual Functionality of ROS
2.2. Major Producers of ROS in the Reproductive System
2.3. Effects of Oxidative Imbalance on the Reproductive System
2.4. Wider Implications of Oxidative Stress on Sperm Health and Reproductive Potential
2.4.1. Effects of Oxidative Stress on Sperm Parameters
2.4.2. Effects of Oxidative Stress on Reproductive Potential
3. Antioxidants and Reproductive Health
- Enzymatic Antioxidants: These include enzymes like superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPx) and are central to combating oxidative stress by breaking down harmful ROS into harmless components [53].
- Nonenzymatic Antioxidants: This broad group encompasses vitamins, minerals, carotenoids, and flavonoids. Notable examples include vitamins C and E, which neutralize free radicals, and minerals like selenium and zinc that support enzymatic antioxidants. Dietary carotenoids and flavonoids further fortify the body’s antioxidant defenses [54].
- Fruits and Vegetables: Berries offer anthocyanins, citrus fruits are a source of vitamin C, and vegetables such as tomatoes and spinach deliver a blend of vitamins and other antioxidant compounds [55].
- Nuts and Seeds: Sources of essential nutrients, including antioxidants. Examples include almonds with vitamin E and flaxseeds rich in lignans [56].
- Whole Grains: Besides fiber, grains like brown rice and quinoa offer antioxidants such as selenium [57].
- Legumes: Beans and lentils, rich in flavonoids, contribute antioxidants alongside their other nutritional benefits [58].
- Herbs and Spices: Flavor enhancers like turmeric, cinnamon, and garlic are also potent sources of antioxidants [59].
4. Antioxidants Supplements and Male Fertility Enhancement
4.1. Role of Antioxidant Supplementation in Male Reproduction
4.1.1. Positive Effects on Sperm Health
4.1.2. Fertility Outcomes and Antioxidant Supplementation
4.2. Common Antioxidants Used in Dietary Supplementation
4.2.1. Vitamin Supplements
4.2.2. Zinc
4.2.3. Selenium
4.2.4. Coenzyme Q10
4.2.5. L-Carnitine
4.2.6. L-Arginine
4.2.7. Lycopene
4.2.8. Inositols
4.2.9. Alpha-Lipoic Acid
4.2.10. Considerations for the Dosage, Duration, and Potential Side Effects of Antioxidant Supplementation
4.2.11. Exploring the Synergy of Multiple Antioxidants
5. Antioxidants in Clinical Perspective: A Therapeutic Beacon
6. Conclusions
Funding
Conflicts of Interest
References
- Kumar, N.; Singh, A.K. Trends of male factor infertility, an important cause of infertility: A review of literature. J. Hum. Reprod. Sci. 2015, 8, 191–196. [Google Scholar] [CrossRef]
- Schieber, M.; Chandel, N.S. ROS function in redox signaling and oxidative stress. Curr. Biol. 2014, 24, R453–R462. [Google Scholar] [CrossRef] [PubMed]
- Pizzino, G.; Irrera, N.; Cucinotta, M.; Pallio, G.; Mannino, F.; Arcoraci, V.; Squadrito, F.; Altavilla, D.; Bitto, A. Oxidative Stress: Harms and Benefits for Human Health. Oxid. Med. Cell Longev. 2017, 2017, 8416763. [Google Scholar] [CrossRef] [PubMed]
- Castleton, P.E.; Deluao, J.C.; Sharkey, D.J.; McPherson, N.O. Measuring Reactive Oxygen Species in Semen for Male Preconception Care: A Scientist Perspective. Antioxidants 2022, 11, 264. [Google Scholar] [CrossRef] [PubMed]
- O’Flaherty, C. Reactive Oxygen Species and Male Fertility. Antioxidants 2020, 9, 287. [Google Scholar] [CrossRef]
- Alahmar, A.T. Role of Oxidative Stress in Male Infertility: An Updated Review. J. Hum. Reprod. Sci. 2019, 12, 4–18. [Google Scholar] [CrossRef]
- Agarwal, A.; Parekh, N.; Panner Selvam, M.K.; Henkel, R.; Shah, R.; Homa, S.T.; Ramasamy, R.; Ko, E.; Tremellen, K.; Esteves, S.; et al. Male Oxidative Stress Infertility (MOSI): Proposed Terminology and Clinical Practice Guidelines for Management of Idiopathic Male Infertility. World J. Mens Health 2019, 37, 296–312. [Google Scholar] [CrossRef]
- Lu, J.M.; Lin, P.H.; Yao, Q.; Chen, C. Chemical and molecular mechanisms of antioxidants: Experimental approaches and model systems. J. Cell Mol. Med. 2010, 14, 840–860. [Google Scholar] [CrossRef]
- Kefer, J.C.; Agarwal, A.; Sabanegh, E. Role of antioxidants in the treatment of male infertility. Int. J. Urol. 2009, 16, 449–457. [Google Scholar] [CrossRef]
- Agarwal, A.; Roychoudhury, S.; Bjugstad, K.B.; Cho, C.L. Oxidation-reduction potential of semen: What is its role in the treatment of male infertility? Ther. Adv. Urol. 2016, 8, 302–318. [Google Scholar] [CrossRef]
- Mannucci, A.; Argento, F.R.; Fini, E.; Coccia, M.E.; Taddei, N.; Becatti, M.; Fiorillo, C. The Impact of Oxidative Stress in Male Infertility. Front. Mol. Biosci. 2021, 8, 799294. [Google Scholar] [CrossRef] [PubMed]
- Checa, J.; Aran, J.M. Reactive Oxygen Species: Drivers of Physiological and Pathological Processes. J. Inflamm. Res. 2020, 13, 1057–1073. [Google Scholar] [CrossRef]
- De Lamirande, E.; Jiang, H.; Zini, A.; Kodama, H.; Gagnon, C. Reactive oxygen species and sperm physiology. Rev. Reprod. 1997, 2, 48–54. [Google Scholar] [CrossRef]
- Bansal, A.K.; Bilaspuri, G.S. Impacts of oxidative stress and antioxidants on semen functions. Vet. Med. Int. 2010, 2010, 686137. [Google Scholar] [CrossRef]
- Darbandi, M.; Darbandi, S.; Agarwal, A.; Sengupta, P.; Durairajanayagam, D.; Henkel, R.; Sadeghi, M.R. Reactive oxygen species and male reproductive hormones. Reprod. Biol. Endocrinol. 2018, 16, 87. [Google Scholar] [CrossRef] [PubMed]
- Aitken, R.J.; Drevet, J.R.; Moazamian, A.; Gharagozloo, P. Male Infertility and Oxidative Stress: A Focus on the Underlying Mechanisms. Antioxidants 2022, 11, 306. [Google Scholar] [CrossRef]
- Sanocka, D.; Kurpisz, M. Reactive oxygen species and sperm cells. Reprod. Biol. Endocrinol. 2004, 2, 12. [Google Scholar] [CrossRef]
- Li, X.; Ni, M.; Xing, S.; Yu, Y.; Zhou, Y.; Yang, S.; Li, H.; Zhu, R.; Han, M. Reactive Oxygen Species Secreted by Leukocytes in Semen Induce Self-Expression of Interleukin-6 and Affect Sperm Quality. Am. J. Mens Health 2020, 14, 1557988320970053. [Google Scholar] [CrossRef] [PubMed]
- Chen, L.; Deng, H.; Cui, H.; Fang, J.; Zuo, Z.; Deng, J.; Li, Y.; Wang, X.; Zhao, L. Inflammatory responses and inflammation-associated diseases in organs. Oncotarget 2018, 9, 7204–7218. [Google Scholar] [CrossRef] [PubMed]
- Sharifi-Rad, M.; Anil Kumar, N.V.; Zucca, P.; Varoni, E.M.; Dini, L.; Panzarini, E.; Rajkovic, J.; Tsouh Fokou, P.V.; Azzini, E.; Peluso, I.; et al. Lifestyle, Oxidative Stress, and Antioxidants: Back and Forth in the Pathophysiology of Chronic Diseases. Front. Physiol. 2020, 11, 694. [Google Scholar] [CrossRef]
- Aitken, R.J.; Drevet, J.R. The Importance of Oxidative Stress in Determining the Functionality of Mammalian Spermatozoa: A Two-Edged Sword. Antioxidants 2020, 9, 111. [Google Scholar] [CrossRef] [PubMed]
- Hosen, M.B.; Islam, M.R.; Begum, F.; Kabir, Y.; Howlader, M.Z. Oxidative stress induced sperm DNA damage, a possible reason for male infertility. Iran J. Reprod. Med. 2015, 13, 525–532. [Google Scholar] [PubMed]
- González-Marín, C.; Gosálvez, J.; Roy, R. Types, Causes, Detection and Repair of DNA Fragmentation in Animal and Human Sperm Cells. Int. J. Mol. Sci. 2012, 13, 14026–14052. [Google Scholar] [CrossRef] [PubMed]
- Rashki Ghaleno, L.; Alizadeh, A.; Drevet, J.R.; Shahverdi, A.; Valojerdi, M.R. Oxidation of Sperm DNA and Male Infertility. Antioxidants 2021, 10, 97. [Google Scholar] [CrossRef]
- Nowicka-Bauer, K.; Nixon, B. Molecular Changes Induced by Oxidative Stress that Impair Human Sperm Motility. Antioxidants 2020, 9, 134. [Google Scholar] [CrossRef]
- Piomboni, P.; Focarelli, R.; Stendardi, A.; Ferramosca, A.; Zara, V. The role of mitochondria in energy production for human sperm motility. Int. J. Androl. 2012, 35, 109–124. [Google Scholar] [CrossRef]
- Durairajanayagam, D.; Singh, D.; Agarwal, A.; Henkel, R. Causes and consequences of sperm mitochondrial dysfunction. Andrologia 2021, 53, e13666. [Google Scholar] [CrossRef]
- Agarwal, A.; Virk, G.; Ong, C.; du Plessis, S.S. Effect of oxidative stress on male reproduction. World J. Mens Health 2014, 32, 1–17. [Google Scholar] [CrossRef]
- La Vignera, S.; Condorelli, R.; Vicari, E.; D’Agata, R.; Calogero, A.E. Diabetes mellitus and sperm parameters. J. Androl. 2012, 33, 145–153. [Google Scholar] [CrossRef]
- Walczak-Jedrzejowska, R.; Wolski, J.K.; Slowikowska-Hilczer, J. The role of oxidative stress and antioxidants in male fertility. Cent. European J. Urol. 2013, 66, 60–67. [Google Scholar] [CrossRef]
- Bui, A.D.; Sharma, R.; Henkel, R.; Agarwal, A. Reactive oxygen species impact on sperm DNA and its role in male infertility. Andrologia 2018, 50, e13012. [Google Scholar] [CrossRef] [PubMed]
- Aitken, R.J.; Smith, T.B.; Jobling, M.S.; Baker, M.A.; De Iuliis, G.N. Oxidative stress and male reproductive health. Asian J. Androl. 2014, 16, 31–38. [Google Scholar] [CrossRef]
- Ribas-Maynou, J.; Yeste, M. Oxidative Stress in Male Infertility: Causes, Effects in Assisted Reproductive Techniques, and Protective Support of Antioxidants. Biology 2020, 9, 77. [Google Scholar] [CrossRef] [PubMed]
- Cannarella, R.; Crafa, A.; Barbagallo, F.; Mongioi, L.M.; Condorelli, R.A.; Aversa, A.; Calogero, A.E.; La Vignera, S. Seminal Plasma Proteomic Biomarkers of Oxidative Stress. Int. J. Mol. Sci. 2020, 21, 9113. [Google Scholar] [CrossRef] [PubMed]
- Dutta, S.; Majzoub, A.; Agarwal, A. Oxidative stress and sperm function: A systematic review on evaluation and management. Arab J. Urol. 2019, 17, 87–97. [Google Scholar] [CrossRef]
- Gualtieri, R.; Kalthur, G.; Barbato, V.; Longobardi, S.; Di Rella, F.; Adiga, S.K.; Talevi, R. Sperm Oxidative Stress during In Vitro Manipulation and Its Effects on Sperm Function and Embryo Development. Antioxidants 2021, 10, 1025. [Google Scholar] [CrossRef] [PubMed]
- Chianese, R.; Pierantoni, R. Mitochondrial Reactive Oxygen Species (ROS) Production Alters Sperm Quality. Antioxidants 2021, 10, 92. [Google Scholar] [CrossRef]
- Jakubik-Uljasz, J.; Gill, K.; Rosiak-Gill, A.; Piasecka, M. Relationship between sperm morphology and sperm DNA dispersion. Transl. Androl. Urol. 2020, 9, 405–415. [Google Scholar] [CrossRef]
- Qiu, Y.; Yang, H.; Li, C.; Xu, C. Progress in Research on Sperm DNA Fragmentation. Med. Sci. Monit. 2020, 26, e918746. [Google Scholar] [CrossRef] [PubMed]
- Drevet, J.R.; Aitken, R.J. Oxidation of Sperm Nucleus in Mammals: A Physiological Necessity to Some Extent with Adverse Impacts on Oocyte and Offspring. Antioxidants 2020, 9, 95. [Google Scholar] [CrossRef]
- O’Flaherty, C. Redox regulation of mammalian sperm capacitation. Asian J Androl 2015, 17, 583–590. [Google Scholar] [CrossRef]
- Radomil, L.; Pettitt, M.J.; Merkies, K.M.; Hickey, K.D.; Buhr, M.M. Stress and dietary factors modify boar sperm for processing. Reprod. Domest. Anim. 2011, 46 (Suppl. 2), 39–44. [Google Scholar] [CrossRef] [PubMed]
- Fujii, J.; Tsunoda, S. Redox regulation of fertilisation and the spermatogenic process. Asian J. Androl. 2011, 13, 420–423. [Google Scholar] [CrossRef]
- Du Plessis, S.S.; Agarwal, A.; Halabi, J.; Tvrda, E. Contemporary evidence on the physiological role of reactive oxygen species in human sperm function. J. Assist Reprod. Genet. 2015, 32, 509–520. [Google Scholar] [CrossRef]
- Aitken, R.J. Reactive oxygen species as mediators of sperm capacitation and pathological damage. Mol. Reprod. Dev. 2017, 84, 1039–1052. [Google Scholar] [CrossRef] [PubMed]
- Aitken, R.J.; Baker, M.A.; Nixon, B. Are sperm capacitation and apoptosis the opposite ends of a continuum driven by oxidative stress? Asian J. Androl. 2015, 17, 633–639. [Google Scholar] [CrossRef]
- Suarez, S.S. Control of hyperactivation in sperm. Hum. Reprod. Update 2008, 14, 647–657. [Google Scholar] [CrossRef]
- Griveau, J.F.; Le Lannou, D. Reactive oxygen species and human spermatozoa: Physiology and pathology. Int. J. Androl. 1997, 20, 61–69. [Google Scholar] [CrossRef]
- Khosrowbeygi, A.; Zarghami, N. Fatty acid composition of human spermatozoa and seminal plasma levels of oxidative stress biomarkers in subfertile males. Prostaglandins Leukot. Essent. Fat. Acids 2007, 77, 117–121. [Google Scholar] [CrossRef]
- Kaltsas, A.; Zikopoulos, A.; Moustakli, E.; Zachariou, A.; Tsirka, G.; Tsiampali, C.; Palapela, N.; Sofikitis, N.; Dimitriadis, F. The Silent Threat to Women’s Fertility: Uncovering the Devastating Effects of Oxidative Stress. Antioxidants 2023, 12, 1490. [Google Scholar] [CrossRef]
- Rima, D.; Shiv, B.K.; Bhavna, C.; Shilpa, B.; Saima, K. Oxidative Stress Induced Damage to Paternal Genome and Impact of Meditation and Yoga—Can it Reduce Incidence of Childhood Cancer? Asian Pac. J. Cancer Prev. 2016, 17, 4517–4525. [Google Scholar] [PubMed]
- Kaltsas, A.; Moustakli, E.; Zikopoulos, A.; Georgiou, I.; Dimitriadis, F.; Symeonidis, E.N.; Markou, E.; Michaelidis, T.M.; Tien, D.M.B.; Giannakis, I.; et al. Impact of Advanced Paternal Age on Fertility and Risks of Genetic Disorders in Offspring. Genes 2023, 14, 486. [Google Scholar] [CrossRef]
- Ighodaro, O.M.; Akinloye, O.A. First line defence antioxidants-superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX): Their fundamental role in the entire antioxidant defence grid. Alex. J. Med. 2018, 54, 287–293. [Google Scholar] [CrossRef]
- Lobo, V.; Patil, A.; Phatak, A.; Chandra, N. Free radicals, antioxidants and functional foods: Impact on human health. Pharmacogn. Rev. 2010, 4, 118–126. [Google Scholar] [CrossRef]
- Slavin, J.L.; Lloyd, B. Health benefits of fruits and vegetables. Adv. Nutr. 2012, 3, 506–516. [Google Scholar] [CrossRef]
- Ros, E. Health benefits of nut consumption. Nutrients 2010, 2, 652–682. [Google Scholar] [CrossRef] [PubMed]
- Jonnalagadda, S.S.; Harnack, L.; Hai Liu, R.; McKeown, N.; Seal, C.; Liu, S.; Fahey, G.C. Putting the Whole Grain Puzzle Together: Health Benefits Associated with Whole Grains—Summary of American Society for Nutrition 2010 Satellite Symposium1–3. J. Nutr. 2011, 141, 1011S–1022S. [Google Scholar] [CrossRef]
- Mullins, A.P.; Arjmandi, B.H. Health Benefits of Plant-Based Nutrition: Focus on Beans in Cardiometabolic Diseases. Nutrients 2021, 13, 519. [Google Scholar] [CrossRef]
- Prasad, S.; Aggarwal, B.B. Turmeric, the Golden Spice: From Traditional Medicine to Modern Medicine. In Herbal Medicine: Biomolecular and Clinical Aspects, 2nd ed.; Benzie, I.F.F., Wachtel-Galor, S., Eds.; CRC Press: Boca Raton, FL, USA, 2011. [Google Scholar]
- Poljsak, B.; Šuput, D.; Milisav, I. Achieving the Balance between ROS and Antioxidants: When to Use the Synthetic Antioxidants. Oxidative Med. Cell. Longev. 2013, 2013, 956792. [Google Scholar] [CrossRef] [PubMed]
- Martin-Hidalgo, D.; Bragado, M.J.; Batista, A.R.; Oliveira, P.F.; Alves, M.G. Antioxidants and Male Fertility: From Molecular Studies to Clinical Evidence. Antioxidants 2019, 8, 89. [Google Scholar] [CrossRef]
- De Luca, M.N.; Colone, M.; Gambioli, R.; Stringaro, A.; Unfer, V. Oxidative Stress and Male Fertility: Role of Antioxidants and Inositols. Antioxidants 2021, 10, 1283. [Google Scholar] [CrossRef]
- Noegroho, B.S.; Siregar, S.; Tampubolon, K.A.G. Antioxidant Supplementation on Sperm DNA Fragmentation and Sperm Parameters: A Systematic Review and Meta-Analysis. Turk J. Urol. 2022, 48, 375–384. [Google Scholar] [CrossRef]
- Li, K.-P.; Yang, X.-S.; Wu, T. The Effect of Antioxidants on Sperm Quality Parameters and Pregnancy Rates for Idiopathic Male Infertility: A Network Meta-Analysis of Randomized Controlled Trials. Front. Endocrinol. 2022, 13, 810242. [Google Scholar] [CrossRef] [PubMed]
- Evans, E.P.P.; Scholten, J.T.M.; Mzyk, A.; Reyes-San-Martin, C.; Llumbet, A.E.; Hamoh, T.; Arts, E.G.J.M.; Schirhagl, R.; Cantineau, A.E.P. Male subfertility and oxidative stress. Redox Biol. 2021, 46, 102071. [Google Scholar] [CrossRef]
- Sadaghiani, S.; Fallahi, S.; Heshmati, H.; Teshnizi, S.H.; Chaijan, H.A.; Ebrahimi, F.F.A.; Khorrami, F.; Poorrezaeian, M.; Alizadeh, F. Effect of antioxidant supplements on sperm parameters in infertile male smokers: A single-blinded clinical trial. AIMS Public Health 2020, 7, 92–99. [Google Scholar] [CrossRef]
- Qazi, I.H.; Angel, C.; Yang, H.; Zoidis, E.; Pan, B.; Wu, Z.; Ming, Z.; Zeng, C.-J.; Meng, Q.; Han, H.; et al. Role of Selenium and Selenoproteins in Male Reproductive Function: A Review of Past and Present Evidences. Antioxidants 2019, 8, 268. [Google Scholar] [CrossRef] [PubMed]
- Peris-Frau, P.; Soler, A.J.; Iniesta-Cuerda, M.; Martin-Maestro, A.; Sanchez-Ajofrin, I.; Medina-Chavez, D.A.; Fernandez-Santos, M.R.; Garcia-Alvarez, O.; Maroto-Morales, A.; Montoro, V.; et al. Sperm Cryodamage in Ruminants: Understanding the Molecular Changes Induced by the Cryopreservation Process to Optimize Sperm Quality. Int. J. Mol. Sci. 2020, 21, 2781. [Google Scholar] [CrossRef] [PubMed]
- Gholami-Ahangaran, M.; Karimi-Dehkordi, M.; Akbari Javar, A.; Haj Salehi, M.; Ostadpoor, M. A systematic review on the effect of Ginger (Zingiber officinale) on improvement of biological and fertility indices of sperm in laboratory animals, poultry and humans. Vet. Med. Sci. 2021, 7, 1959–1969. [Google Scholar] [CrossRef] [PubMed]
- Silver, E.W.; Eskenazi, B.; Evenson, D.P.; Block, G.; Young, S.; Wyrobek, A.J. Effect of antioxidant intake on sperm chromatin stability in healthy nonsmoking men. J. Androl. 2005, 26, 550–556. [Google Scholar] [CrossRef]
- Sikka, S.C. Oxidative stress and role of antioxidants in normal and abnormal sperm function. Front. Biosci. 1996, 1, e78–e86. [Google Scholar] [CrossRef]
- Dimitriadis, F.; Borgmann, H.; Struck, J.P.; Salem, J.; Kuru, T.H. Antioxidant Supplementation on Male Fertility—A Systematic Review. Antioxidants 2023, 12, 836. [Google Scholar] [CrossRef]
- Yan, J.; De Melo, J.; Cutz, J.C.; Aziz, T.; Tang, D. Aldehyde dehydrogenase 3A1 associates with prostate tumorigenesis. Br. J. Cancer 2014, 110, 2593–2603. [Google Scholar] [CrossRef]
- Therond, P.; Auger, J.; Legrand, A.; Jouannet, P. alpha-Tocopherol in human spermatozoa and seminal plasma: Relationships with motility, antioxidant enzymes and leukocytes. Mol. Hum. Reprod. 1996, 2, 739–744. [Google Scholar] [CrossRef] [PubMed]
- Ener, K.; Aldemir, M.; Isik, E.; Okulu, E.; Ozcan, M.F.; Ugurlu, M.; Tangal, S.; Ozayar, A. The impact of vitamin E supplementation on semen parameters and pregnancy rates after varicocelectomy: A randomised controlled study. Andrologia 2016, 48, 829–834. [Google Scholar] [CrossRef] [PubMed]
- Omu, A.E.; Fatinikun, T.; Mannazhath, N.; Abraham, S. Significance of simultaneous determination of serum and seminal plasma alpha-tocopherol and retinol in infertile men by high-performance liquid chromatography. Andrologia 1999, 31, 347–354. [Google Scholar] [CrossRef] [PubMed]
- Geva, E.; Bartoov, B.; Zabludovsky, N.; Lessing, J.B.; Lerner-Geva, L.; Amit, A. The effect of antioxidant treatment on human spermatozoa and fertilization rate in an in vitro fertilization program. Fertil. Steril. 1996, 66, 430–434. [Google Scholar] [CrossRef]
- Kodama, H.; Yamaguchi, R.; Fukuda, J.; Kasai, H.; Tanaka, T. Increased oxidative deoxyribonucleic acid damage in the spermatozoa of infertile male patients. Fertil. Steril. 1997, 68, 519–524. [Google Scholar] [CrossRef]
- Vezina, D.; Mauffette, F.; Roberts, K.D.; Bleau, G. Selenium-vitamin E supplementation in infertile men. Effects on semen parameters and micronutrient levels and distribution. Biol. Trace Elem. Res. 1996, 53, 65–83. [Google Scholar] [CrossRef]
- Sinclair, S. Male infertility: Nutritional and environmental considerations. Altern. Med. Rev. 2000, 5, 28–38. [Google Scholar]
- Comhaire, F.H.; Christophe, A.B.; Zalata, A.A.; Dhooge, W.S.; Mahmoud, A.M.; Depuydt, C.E. The effects of combined conventional treatment, oral antioxidants and essential fatty acids on sperm biology in subfertile men. Prostaglandins Leukot. Essent. Fat. Acids 2000, 63, 159–165. [Google Scholar] [CrossRef]
- Agarwal, A.; Nallella, K.P.; Allamaneni, S.S.; Said, T.M. Role of antioxidants in treatment of male infertility: An overview of the literature. Reprod. Biomed. Online 2004, 8, 616–627. [Google Scholar] [CrossRef]
- Greco, E.; Iacobelli, M.; Rienzi, L.; Ubaldi, F.; Ferrero, S.; Tesarik, J. Reduction of the incidence of sperm DNA fragmentation by oral antioxidant treatment. J. Androl. 2005, 26, 349–353. [Google Scholar] [CrossRef] [PubMed]
- Ross, C.; Morriss, A.; Khairy, M.; Khalaf, Y.; Braude, P.; Coomarasamy, A.; El-Toukhy, T. A systematic review of the effect of oral antioxidants on male infertility. Reprod. Biomed. Online 2010, 20, 711–723. [Google Scholar] [CrossRef] [PubMed]
- Moslemi, M.K.; Tavanbakhsh, S. Selenium-vitamin E supplementation in infertile men: Effects on semen parameters and pregnancy rate. Int. J. Gen. Med. 2011, 4, 99–104. [Google Scholar] [CrossRef]
- Lombardo, F.; Sansone, A.; Romanelli, F.; Paoli, D.; Gandini, L.; Lenzi, A. The role of antioxidant therapy in the treatment of male infertility: An overview. Asian J. Androl. 2011, 13, 690–697. [Google Scholar] [CrossRef] [PubMed]
- Brigelius-Flohe, R.; Traber, M.G. Vitamin E: Function and metabolism. FASEB J. 1999, 13, 1145–1155. [Google Scholar] [CrossRef]
- Rengaraj, D.; Hong, Y.H. Effects of dietary vitamin E on fertility functions in poultry species. Int. J. Mol. Sci. 2015, 16, 9910–9921. [Google Scholar] [CrossRef]
- Kessopoulou, E.; Powers, H.J.; Sharma, K.K.; Pearson, M.J.; Russell, J.M.; Cooke, I.D.; Barratt, C.L. A double-blind randomized placebo cross-over controlled trial using the antioxidant vitamin E to treat reactive oxygen species associated male infertility. Fertil. Steril. 1995, 64, 825–831. [Google Scholar] [CrossRef]
- Brzozowski, T.; Kwiecien, S.; Konturek, P.C.; Konturek, S.J.; Mitis-Musiol, M.; Duda, A.; Bielanski, W.; Hahn, E.G. Comparison of nitric oxide-releasing NSAID and vitamin C with classic NSAID in healing of chronic gastric ulcers; involvement of reactive oxygen species. Med. Sci. Monit. 2001, 7, 592–599. [Google Scholar] [PubMed]
- Behairy, A.; El-Sharkawy, N.I.; Saber, T.M.; Soliman, M.M.; Metwally, M.M.M.; Abd El-Rahman, G.I.; Abd-Elhakim, Y.M.; El Deib, M.M. The Modulatory Role of Vitamin C in Boldenone Undecylenate Induced Testicular Oxidative Damage and Androgen Receptor Dysregulation in Adult Male Rats. Antioxidants 2020, 9, 1053. [Google Scholar] [CrossRef] [PubMed]
- Seo, M.Y.; Lee, S.M. Protective effect of low dose of ascorbic acid on hepatobiliary function in hepatic ischemia/reperfusion in rats. J. Hepatol. 2002, 36, 72–77. [Google Scholar] [CrossRef] [PubMed]
- Zini, A.; Albert, O.; Robaire, B. Assessing sperm chromatin and DNA damage: Clinical importance and development of standards. Andrology 2014, 2, 322–325. [Google Scholar] [CrossRef]
- Jacob, R.A.; Pianalto, F.S.; Agee, R.E. Cellular ascorbate depletion in healthy men. J. Nutr. 1992, 122, 1111–1118. [Google Scholar] [CrossRef] [PubMed]
- Colagar, A.H.; Marzony, E.T. Ascorbic Acid in human seminal plasma: Determination and its relationship to sperm quality. J. Clin. Biochem. Nutr. 2009, 45, 144–149. [Google Scholar] [CrossRef] [PubMed]
- Fraga, C.G.; Motchnik, P.A.; Shigenaga, M.K.; Helbock, H.J.; Jacob, R.A.; Ames, B.N. Ascorbic acid protects against endogenous oxidative DNA damage in human sperm. Proc. Natl. Acad. Sci. USA 1991, 88, 11003–11006. [Google Scholar] [CrossRef]
- Lewis, S.E.; John Aitken, R.; Conner, S.J.; Iuliis, G.D.; Evenson, D.P.; Henkel, R.; Giwercman, A.; Gharagozloo, P. The impact of sperm DNA damage in assisted conception and beyond: Recent advances in diagnosis and treatment. Reprod. Biomed. Online 2013, 27, 325–337. [Google Scholar] [CrossRef]
- Iqbal, K.; Khan, A.; Khattak, M. Biological significance of ascorbic acid (vitamin C) in human health-a review. Pak. J. Nutr. 2004, 3, 5–13. [Google Scholar]
- Wagner, A.E.; Huebbe, P.; Konishi, T.; Rahman, M.M.; Nakahara, M.; Matsugo, S.; Rimbach, G. Free radical scavenging and antioxidant activity of ascorbigen versus ascorbic acid: Studies in vitro and in cultured human keratinocytes. J. Agric. Food Chem. 2008, 56, 11694–11699. [Google Scholar] [CrossRef]
- Mangoli, E.; Talebi, A.R.; Anvari, M.; Taheri, F.; Vatanparast, M.; Rahiminia, T.; Hosseini, A. Vitamin C attenuates negative effects of vitrification on sperm parameters, chromatin quality, apoptosis and acrosome reaction in neat and prepared normozoospermic samples. Taiwan J. Obstet. Gynecol. 2018, 57, 200–204. [Google Scholar] [CrossRef]
- Acharya, U.R.; Mishra, M.; Patro, J.; Panda, M.K. Effect of vitamins C and E on spermatogenesis in mice exposed to cadmium. Reprod. Toxicol. 2008, 25, 84–88. [Google Scholar] [CrossRef]
- Cyrus, A.; Kabir, A.; Goodarzi, D.; Moghimi, M. The effect of adjuvant vitamin C after varicocele surgery on sperm quality and quantity in infertile men: A double blind placebo controlled clinical trial. Int. Braz. J. Urol. 2015, 41, 230–238. [Google Scholar] [CrossRef]
- Hajjar, T.; Soleymani, F.; Vatanchian, M. Protective Effect of Vitamin C and Zinc as an Antioxidant Against Chemotherapy-Induced Male Reproductive Toxicity. J. Med. Life 2020, 13, 138–143. [Google Scholar] [CrossRef]
- Boachie, J.; Adaikalakoteswari, A.; Samavat, J.; Saravanan, P. Low Vitamin B12 and Lipid Metabolism: Evidence from Pre-Clinical and Clinical Studies. Nutrients 2020, 12, 1925. [Google Scholar] [CrossRef] [PubMed]
- Banihani, S.A. Vitamin B(12) and Semen Quality. Biomolecules 2017, 7, 42. [Google Scholar] [CrossRef] [PubMed]
- Hosseinabadi, F.; Jenabi, M.; Ghafarizadeh, A.A.; Yazdanikhah, S. The effect of vitamin B12 supplement on post-thaw motility, viability and DNA damage of human sperm. Andrologia 2020, 52, e13877. [Google Scholar] [CrossRef]
- Berridge, M.J. Vitamin D deficiency: Infertility and neurodevelopmental diseases (attention deficit hyperactivity disorder, autism, and schizophrenia). Am. J. Physiol. Cell Physiol. 2018, 314, C135–C151. [Google Scholar] [CrossRef] [PubMed]
- Boisen, I.M.; Bollehuus Hansen, L.; Mortensen, L.J.; Lanske, B.; Juul, A.; Blomberg Jensen, M. Possible influence of vitamin D on male reproduction. J. Steroid Biochem. Mol. Biol. 2017, 173, 215–222. [Google Scholar] [CrossRef]
- Blomberg Jensen, M.; Gerner Lawaetz, J.; Andersson, A.M.; Petersen, J.H.; Nordkap, L.; Bang, A.K.; Ekbom, P.; Joensen, U.N.; Praetorius, L.; Lundstrom, P.; et al. Vitamin D deficiency and low ionized calcium are linked with semen quality and sex steroid levels in infertile men. Hum. Reprod. 2016, 31, 1875–1885. [Google Scholar] [CrossRef]
- Tartagni, M.; Matteo, M.; Baldini, D.; Tartagni, M.V.; Alrasheed, H.; De Salvia, M.A.; Loverro, G.; Montagnani, M. Males with low serum levels of vitamin D have lower pregnancy rates when ovulation induction and timed intercourse are used as a treatment for infertile couples: Results from a pilot study. Reprod. Biol. Endocrinol. 2015, 13, 127. [Google Scholar] [CrossRef]
- Ozkan, S.; Jindal, S.; Greenseid, K.; Shu, J.; Zeitlian, G.; Hickmon, C.; Pal, L. Replete vitamin D stores predict reproductive success following in vitro fertilization. Fertil. Steril. 2010, 94, 1314–1319. [Google Scholar] [CrossRef]
- Pacis, M.M.; Fortin, C.N.; Zarek, S.M.; Mumford, S.L.; Segars, J.H. Vitamin D and assisted reproduction: Should vitamin D be routinely screened and repleted prior to ART? A systematic review. J. Assist Reprod. Genet. 2015, 32, 323–335. [Google Scholar] [CrossRef]
- Skowronska, P.; Pastuszek, E.; Kuczynski, W.; Jaszczol, M.; Kuc, P.; Jakiel, G.; Woclawek-Potocka, I.; Lukaszuk, K. The role of vitamin D in reproductive dysfunction in women—A systematic review. Ann. Agric. Environ. Med. 2016, 23, 671–676. [Google Scholar] [CrossRef]
- Joshi, R.; Adhikari, S.; Patro, B.S.; Chattopadhyay, S.; Mukherjee, T. Free radical scavenging behavior of folic acid: Evidence for possible antioxidant activity. Free Radic. Biol. Med. 2001, 30, 1390–1399. [Google Scholar] [CrossRef] [PubMed]
- Nematollahi-Mahani, S.N.; Azizollahi, G.H.; Baneshi, M.R.; Safari, Z.; Azizollahi, S. Effect of folic acid and zinc sulphate on endocrine parameters and seminal antioxidant level after varicocelectomy. Andrologia 2014, 46, 240–245. [Google Scholar] [CrossRef] [PubMed]
- Raigani, M.; Yaghmaei, B.; Amirjannti, N.; Lakpour, N.; Akhondi, M.M.; Zeraati, H.; Hajihosseinal, M.; Sadeghi, M.R. The micronutrient supplements, zinc sulphate and folic acid, did not ameliorate sperm functional parameters in oligoasthenoteratozoospermic men. Andrologia 2014, 46, 956–962. [Google Scholar] [CrossRef] [PubMed]
- Irani, M.; Amirian, M.; Sadeghi, R.; Lez, J.L.; Latifnejad Roudsari, R. The Effect of Folate and Folate Plus Zinc Supplementation on Endocrine Parameters and Sperm Characteristics in Sub-Fertile Men: A Systematic Review and Meta-Analysis. Urol. J. 2017, 14, 4069–4078. [Google Scholar]
- Khan, M.S.; Zaman, S.; Sajjad, M.; Shoaib, M.; Gilani, G. Assessment of the level of trace element zinc in seminal plasma of males and evaluation of its role in male infertility. Int. J. Appl. Basic Med. Res. 2011, 1, 93–96. [Google Scholar] [CrossRef]
- Hambidge, K.M.; Krebs, N.F. Zinc deficiency: A special challenge. J. Nutr. 2007, 137, 1101–1105. [Google Scholar] [CrossRef]
- Favier, A.E. The role of zinc in reproduction. Hormonal mechanisms. Biol. Trace Elem. Res. 1992, 32, 363–382. [Google Scholar] [CrossRef]
- Powell, S.R. The antioxidant properties of zinc. J. Nutr. 2000, 130, 1447S–1454S. [Google Scholar] [CrossRef]
- Razavi, S.; Khadivi, F.; Hashemi, F.; Bakhtiari, A. Effect of Zinc on Spermatogenesis and Sperm Chromatin Condensation in Bleomycin, Etoposide, Cisplatin Treated Rats. Cell J. 2019, 20, 521–526. [Google Scholar] [CrossRef] [PubMed]
- Batra, N.; Nehru, B.; Bansal, M.P. Influence of lead and zinc on rat male reproduction at ‘biochemical and histopathological levels’. J. Appl. Toxicol. 2001, 21, 507–512. [Google Scholar] [CrossRef] [PubMed]
- Ishizuka, M.; Ohtsuka, E.; Inoue, A.; Odaka, M.; Ohshima, H.; Tamura, N.; Yoshida, K.; Sako, N.; Baba, T.; Kashiwabara, S.; et al. Abnormal spermatogenesis and male infertility in testicular zinc finger protein Zfp318-knockout mice. Dev. Growth Differ. 2016, 58, 600–608. [Google Scholar] [CrossRef] [PubMed]
- Foresta, C.; Garolla, A.; Cosci, I.; Menegazzo, M.; Ferigo, M.; Gandin, V.; De Toni, L. Role of zinc trafficking in male fertility: From germ to sperm. Hum. Reprod. 2014, 29, 1134–1145. [Google Scholar] [CrossRef]
- Fallah, A.; Mohammad-Hasani, A.; Colagar, A.H. Zinc is an Essential Element for Male Fertility: A Review of Zn Roles in Men’s Health, Germination, Sperm Quality, and Fertilization. J. Reprod. Infertil. 2018, 19, 69–81. [Google Scholar] [PubMed]
- Liu, D.Y.; Sie, B.S.; Liu, M.L.; Agresta, F.; Baker, H.W. Relationship between seminal plasma zinc concentration and spermatozoa-zona pellucida binding and the ZP-induced acrosome reaction in subfertile men. Asian J. Androl. 2009, 11, 499–507. [Google Scholar] [CrossRef]
- Cheng, Y.; Chen, H. Aberrance of Zinc Metalloenzymes-Induced Human Diseases and Its Potential Mechanisms. Nutrients 2021, 13, 4456. [Google Scholar] [CrossRef]
- Bjorndahl, L.; Kvist, U. Human sperm chromatin stabilization: A proposed model including zinc bridges. Mol. Hum. Reprod. 2010, 16, 23–29. [Google Scholar] [CrossRef]
- Kothari, R.P.; Chaudhari, A.R. Zinc Levels in Seminal Fluid in Infertile Males and its Relation with Serum Free Testosterone. J Clin. Diagn. Res. 2016, 10, CC05–CC08. [Google Scholar] [CrossRef]
- Colagar, A.H.; Marzony, E.T.; Chaichi, M.J. Zinc levels in seminal plasma are associated with sperm quality in fertile and infertile men. Nutr. Res. 2009, 29, 82–88. [Google Scholar] [CrossRef] [PubMed]
- Alsalman, A.R.S.; Almashhedy, L.A.; Alta’ee, A.H.; Hadwan, M.H. Effect of Zinc Supplementation on Urate Pathway Enzymes in Spermatozoa and Seminal Plasma of Iraqi Asthenozoospermic Patients: A Randomized Controlled Trial. Int. J. Fertil. Steril. 2020, 13, 315–323. [Google Scholar] [CrossRef] [PubMed]
- Ebisch, I.M.; Pierik, F.H.; FH, D.E.J.; Thomas, C.M.; Steegers-Theunissen, R.P. Does folic acid and zinc sulphate intervention affect endocrine parameters and sperm characteristics in men? Int. J. Androl. 2006, 29, 339–345. [Google Scholar] [CrossRef]
- Hadwan, M.H.; Almashhedy, L.A.; Alsalman, A.R. Study of the effects of oral zinc supplementation on peroxynitrite levels, arginase activity and NO synthase activity in seminal plasma of Iraqi asthenospermic patients. Reprod. Biol. Endocrinol. 2014, 12, 1. [Google Scholar] [CrossRef]
- Hadwan, M.H.; Almashhedy, L.A.; Alsalman, A.R. Oral zinc supplementation restores high molecular weight seminal zinc binding protein to normal value in Iraqi infertile men. BMC Urol. 2012, 12, 32. [Google Scholar] [CrossRef]
- Allouche-Fitoussi, D.; Breitbart, H. The Role of Zinc in Male Fertility. Int. J. Mol. Sci. 2020, 21, 7796. [Google Scholar] [CrossRef]
- Pieczynska, J.; Grajeta, H. The role of selenium in human conception and pregnancy. J. Trace Elem. Med. Biol. 2015, 29, 31–38. [Google Scholar] [CrossRef] [PubMed]
- Zhang, Y.; Roh, Y.J.; Han, S.J.; Park, I.; Lee, H.M.; Ok, Y.S.; Lee, B.C.; Lee, S.R. Role of Selenoproteins in Redox Regulation of Signaling and the Antioxidant System: A Review. Antioxidants 2020, 9, 383. [Google Scholar] [CrossRef] [PubMed]
- Tinggi, U. Selenium: Its role as antioxidant in human health. Environ. Health Prev. Med. 2008, 13, 102–108. [Google Scholar] [CrossRef]
- Bjornstedt, M.; Fernandes, A.P. Selenium in the prevention of human cancers. EPMA J. 2010, 1, 389–395. [Google Scholar] [CrossRef]
- Mikhed, Y.; Gorlach, A.; Knaus, U.G.; Daiber, A. Redox regulation of genome stability by effects on gene expression, epigenetic pathways and DNA damage/repair. Redox Biol. 2015, 5, 275–289. [Google Scholar] [CrossRef]
- Mintziori, G.; Mousiolis, A.; Duntas, L.H.; Goulis, D.G. Evidence for a manifold role of selenium in infertility. Hormones 2020, 19, 55–59. [Google Scholar] [CrossRef] [PubMed]
- Foresta, C.; Flohe, L.; Garolla, A.; Roveri, A.; Ursini, F.; Maiorino, M. Male fertility is linked to the selenoprotein phospholipid hydroperoxide glutathione peroxidase. Biol. Reprod. 2002, 67, 967–971. [Google Scholar] [CrossRef] [PubMed]
- Flohe, L. Selenium in mammalian spermiogenesis. Biol. Chem. 2007, 388, 987–995. [Google Scholar] [CrossRef]
- Olson, G.E.; Winfrey, V.P.; Nagdas, S.K.; Hill, K.E.; Burk, R.F. Selenoprotein P is required for mouse sperm development. Biol. Reprod. 2005, 73, 201–211. [Google Scholar] [CrossRef]
- Michaelis, M.; Gralla, O.; Behrends, T.; Scharpf, M.; Endermann, T.; Rijntjes, E.; Pietschmann, N.; Hollenbach, B.; Schomburg, L. Selenoprotein P in seminal fluid is a novel biomarker of sperm quality. Biochem. Biophys. Res. Commun. 2014, 443, 905–910. [Google Scholar] [CrossRef] [PubMed]
- Behne, D.; Hofer, T.; von Berswordt-Wallrabe, R.; Elger, W. Selenium in the testis of the rat: Studies on its regulation and its importance for the organism. J. Nutr. 1982, 112, 1682–1687. [Google Scholar] [CrossRef] [PubMed]
- Behne, D.; Duk, M.; Elger, W. Selenium content and glutathione peroxidase activity in the testis of the maturing rat. J. Nutr. 1986, 116, 1442–1447. [Google Scholar] [CrossRef] [PubMed]
- Bedwal, R.S.; Bahuguna, A. Zinc, copper and selenium in reproduction. Experientia 1994, 50, 626–640. [Google Scholar] [CrossRef]
- Mistry, H.D.; Broughton Pipkin, F.; Redman, C.W.; Poston, L. Selenium in reproductive health. Am. J. Obstet. Gynecol. 2012, 206, 21–30. [Google Scholar] [CrossRef] [PubMed]
- Safarinejad, M.R.; Safarinejad, S. Efficacy of selenium and/or N-acetyl-cysteine for improving semen parameters in infertile men: A double-blind, placebo controlled, randomized study. J. Urol. 2009, 181, 741–751. [Google Scholar] [CrossRef]
- Talebi, S.; Arab, A.; Sorraya, N. The Association Between Dietary Antioxidants and Semen Parameters: A Cross-Sectional Study Among Iranian Infertile Men. Biol. Trace Elem. Res. 2022, 200, 3957–3964. [Google Scholar] [CrossRef]
- Mojadadi, A.; Au, A.; Salah, W.; Witting, P.; Ahmad, G. Role for Selenium in Metabolic Homeostasis and Human Reproduction. Nutrients 2021, 13, 3256. [Google Scholar] [CrossRef]
- Riaz, M.; Mahmood, Z.; Shahid, M.; Saeed, M.U.; Tahir, I.M.; Shah, S.A.; Munir, N.; El-Ghorab, A. Impact of reactive oxygen species on antioxidant capacity of male reproductive system. Int. J. Immunopathol. Pharmacol. 2016, 29, 421–425. [Google Scholar] [CrossRef]
- Sengupta, P.; Dutta, S.; Alahmar, A.T. Reductive Stress and Male Infertility. Adv. Exp. Med. Biol. 2022, 1391, 311–321. [Google Scholar] [CrossRef]
- Sadeghi, N.; Boissonneault, G.; Tavalaee, M.; Nasr-Esfahani, M.H. Oxidative versus reductive stress: A delicate balance for sperm integrity. Syst. Biol. Reprod. Med. 2023, 69, 20–31. [Google Scholar] [CrossRef] [PubMed]
- Cunha, L.; Teixeira, M.Y.P.; Daltro, A.; Torquato, S.E.F.; Assis, R.C.; Celedonio, R.F.; Pires, L.V.; Maia, C.S.C.; Guedes, M.I.F. Unbalance of Se and nutritional status in male infertility. JBRA Assist Reprod. 2021, 25, 202–208. [Google Scholar] [CrossRef] [PubMed]
- Salvio, G.; Cutini, M.; Ciarloni, A.; Giovannini, L.; Perrone, M.; Balercia, G. Coenzyme Q10 and Male Infertility: A Systematic Review. Antioxidants 2021, 10, 874. [Google Scholar] [CrossRef] [PubMed]
- Lafuente, R.; Gonzalez-Comadran, M.; Sola, I.; Lopez, G.; Brassesco, M.; Carreras, R.; Checa, M.A. Coenzyme Q10 and male infertility: A meta-analysis. J. Assist Reprod. Genet. 2013, 30, 1147–1156. [Google Scholar] [CrossRef] [PubMed]
- Sarma, S.; Derose, S.; Govindarajan, N.; Essa, M.M.; Qoronfleh, M.W.; Chidambaram, S.B.; Al-Bulushi, B. Fortification methods of coenzyme Q10 in yogurt and its health functionality-a review. Front. Biosci. 2021, 13, 131–140. [Google Scholar] [CrossRef]
- Lewin, A.; Lavon, H. The effect of coenzyme Q10 on sperm motility and function. Mol. Aspects Med. 1997, 18 (Suppl. 1), S213–S219. [Google Scholar] [CrossRef]
- Mancini, A.; Conte, B.; De Marinis, L.; Hallgass, M.E.; Pozza, D.; Oradei, A.; Littarru, G.P. Coenzyme Q10 levels in human seminal fluid: Diagnostic and clinical implications. Mol Aspects Med 1994, 15 (Suppl. 1), s249–s255. [Google Scholar] [CrossRef] [PubMed]
- Festa, R.; Giacchi, E.; Raimondo, S.; Tiano, L.; Zuccarelli, P.; Silvestrini, A.; Meucci, E.; Littarru, G.P.; Mancini, A. Coenzyme Q10 supplementation in infertile men with low-grade varicocele: An open, uncontrolled pilot study. Andrologia 2014, 46, 805–807. [Google Scholar] [CrossRef] [PubMed]
- Alahmar, A.T.; Calogero, A.E.; Singh, R.; Cannarella, R.; Sengupta, P.; Dutta, S. Coenzyme Q10, oxidative stress, and male infertility: A review. Clin. Exp. Reprod. Med. 2021, 48, 97–104. [Google Scholar] [CrossRef] [PubMed]
- Balercia, G.; Buldreghini, E.; Vignini, A.; Tiano, L.; Paggi, F.; Amoroso, S.; Ricciardo-Lamonica, G.; Boscaro, M.; Lenzi, A.; Littarru, G. Coenzyme Q10 treatment in infertile men with idiopathic asthenozoospermia: A placebo-controlled, double-blind randomized trial. Fertil. Steril. 2009, 91, 1785–1792. [Google Scholar] [CrossRef]
- Nadjarzadeh, A.; Shidfar, F.; Amirjannati, N.; Vafa, M.R.; Motevalian, S.A.; Gohari, M.R.; Nazeri Kakhki, S.A.; Akhondi, M.M.; Sadeghi, M.R. Effect of Coenzyme Q10 supplementation on antioxidant enzymes activity and oxidative stress of seminal plasma: A double-blind randomised clinical trial. Andrologia 2014, 46, 177–183. [Google Scholar] [CrossRef]
- Garcia-Diaz, E.C.; Gomez-Quiroz, L.E.; Arenas-Rios, E.; Aragon-Martinez, A.; Ibarra-Arias, J.A.; del Socorro, I.R.-M.M. Oxidative status in testis and epididymal sperm parameters after acute and chronic stress by cold-water immersion in the adult rat. Syst. Biol. Reprod. Med. 2015, 61, 150–160. [Google Scholar] [CrossRef]
- Gaby, A.R. Re: Effects of the reduced form of coenzyme Q10 (ubiquinol) on semen parameters in men with idiopathic infertility: A double-blind, placebo controlled, randomized study: M. R. Safarinejad, S. Safarinejad, N. Shafiei and S. Safarinejad. J. Urol. 2013, 190, 364–365. [Google Scholar] [CrossRef]
- Thakur, A.S.; Littarru, G.P.; Funahashi, I.; Painkara, U.S.; Dange, N.S.; Chauhan, P. Effect of Ubiquinol Therapy on Sperm Parameters and Serum Testosterone Levels in Oligoasthenozoospermic Infertile Men. J. Clin. Diagn. Res. 2015, 9, BC01–BC03. [Google Scholar] [CrossRef]
- Sukcharoen, N.; Keith, J.; Irvine, D.S.; Aitken, R.J. Predicting the fertilizing potential of human sperm suspensions in vitro: Importance of sperm morphology and leukocyte contamination. Fertil. Steril. 1995, 63, 1293–1300. [Google Scholar] [CrossRef]
- Agarwal, A.; Said, T.M. Carnitines and male infertility. Reprod. Biomed. Online 2004, 8, 376–384. [Google Scholar] [CrossRef]
- Arduini, A.; Bonomini, M.; Savica, V.; Amato, A.; Zammit, V. Carnitine in metabolic disease: Potential for pharmacological intervention. Pharmacol. Ther. 2008, 120, 149–156. [Google Scholar] [CrossRef] [PubMed]
- Banihani, S.; Agarwal, A.; Sharma, R.; Bayachou, M. Cryoprotective effect of L-carnitine on motility, vitality and DNA oxidation of human spermatozoa. Andrologia 2014, 46, 637–641. [Google Scholar] [CrossRef] [PubMed]
- Gulcin, I. Antioxidant and antiradical activities of L-carnitine. Life Sci. 2006, 78, 803–811. [Google Scholar] [CrossRef] [PubMed]
- Ahmed, S.D.; Karira, K.A.; Jagdesh; Ahsan, S. Role of L-carnitine in male infertility. J. Pak. Med. Assoc. 2011, 61, 732–736. [Google Scholar]
- Radigue, C.; Es-Slami, S.; Soufir, J.C. Relationship of carnitine transport across the epididymis to blood carnitine and androgens in rats. Arch Androl. 1996, 37, 27–31. [Google Scholar] [CrossRef]
- Enomoto, A.; Wempe, M.F.; Tsuchida, H.; Shin, H.J.; Cha, S.H.; Anzai, N.; Goto, A.; Sakamoto, A.; Niwa, T.; Kanai, Y.; et al. Molecular identification of a novel carnitine transporter specific to human testis. Insights into the mechanism of carnitine recognition. J. Biol. Chem. 2002, 277, 36262–36271. [Google Scholar] [CrossRef] [PubMed]
- Lenzi, A.; Sgro, P.; Salacone, P.; Paoli, D.; Gilio, B.; Lombardo, F.; Santulli, M.; Agarwal, A.; Gandini, L. A placebo-controlled double-blind randomized trial of the use of combined l-carnitine and l-acetyl-carnitine treatment in men with asthenozoospermia. Fertil. Steril. 2004, 81, 1578–1584. [Google Scholar] [CrossRef]
- Balercia, G.; Regoli, F.; Armeni, T.; Koverech, A.; Mantero, F.; Boscaro, M. Placebo-controlled double-blind randomized trial on the use of L-carnitine, L-acetylcarnitine, or combined L-carnitine and L-acetylcarnitine in men with idiopathic asthenozoospermia. Fertil. Steril. 2005, 84, 662–671. [Google Scholar] [CrossRef]
- Sigman, M.; Glass, S.; Campagnone, J.; Pryor, J.L. Carnitine for the treatment of idiopathic asthenospermia: A randomized, double-blind, placebo-controlled trial. Fertil. Steril. 2006, 85, 1409–1414. [Google Scholar] [CrossRef]
- Garolla, A.; Maiorino, M.; Roverato, A.; Roveri, A.; Ursini, F.; Foresta, C. Oral carnitine supplementation increases sperm motility in asthenozoospermic men with normal sperm phospholipid hydroperoxide glutathione peroxidase levels. Fertil. Steril. 2005, 83, 355–361. [Google Scholar] [CrossRef] [PubMed]
- Srivastava, S.; Desai, P.; Coutinho, E.; Govil, G. Mechanism of action of L-arginine on the vitality of spermatozoa is primarily through increased biosynthesis of nitric oxide. Biol. Reprod. 2006, 74, 954–958. [Google Scholar] [CrossRef] [PubMed]
- Palmer, R.M.; Ashton, D.S.; Moncada, S. Vascular endothelial cells synthesize nitric oxide from L-arginine. Nature 1988, 333, 664–666. [Google Scholar] [CrossRef] [PubMed]
- Moncada, S.; Palmer, R.M.; Higgs, E.A. Nitric oxide: Physiology, pathophysiology, and pharmacology. Pharmacol. Rev. 1991, 43, 109–142. [Google Scholar]
- Zini, A.; De Lamirande, E.; Gagnon, C. Low levels of nitric oxide promote human sperm capacitation in vitro. J. Androl. 1995, 16, 424–431. [Google Scholar] [CrossRef]
- Aitken, R.J.; Paterson, M.; Fisher, H.; Buckingham, D.W.; van Duin, M. Redox regulation of tyrosine phosphorylation in human spermatozoa and its role in the control of human sperm function. J. Cell Sci. 1995, 108 Pt 5, 2017–2025. [Google Scholar] [CrossRef]
- Keller, D.W.; Polakoski, K.L. L-arginine stimulation of human sperm motility in vitro. Biol. Reprod. 1975, 13, 154–157. [Google Scholar] [CrossRef]
- Scibona, M.; Meschini, P.; Capparelli, S.; Pecori, C.; Rossi, P.; Menchini Fabris, G.F. [L-arginine and male infertility]. Minerva Urol. Nefrol. 1994, 46, 251–253. [Google Scholar] [PubMed]
- Srivastava, S.; Desai, P.; Coutinho, E.; Govil, G. Protective effect of L-arginine against lipid peroxidation in goat epididymal spermatozoa. Physiol. Chem. Phys. Med. NMR 2000, 32, 127–135. [Google Scholar]
- Aydin, S.; Inci, O.; Alagol, B. The role of arginine, indomethacin and kallikrein in the treatment of oligoasthenospermia. Int. Urol. Nephrol. 1995, 27, 199–202. [Google Scholar] [CrossRef] [PubMed]
- Stanislavov, R.; Nikolova, V.; Rohdewald, P. Improvement of seminal parameters with Prelox: A randomized, double-blind, placebo-controlled, cross-over trial. Phytother. Res. 2009, 23, 297–302. [Google Scholar] [CrossRef] [PubMed]
- Kelkel, M.; Schumacher, M.; Dicato, M.; Diederich, M. Antioxidant and anti-proliferative properties of lycopene. Free Radic. Res. 2011, 45, 925–940. [Google Scholar] [CrossRef] [PubMed]
- Agarwal, A.; Sekhon, L.H. Oxidative stress and antioxidants for idiopathic oligoasthenoteratospermia: Is it justified? Indian J. Urol. 2011, 27, 74–85. [Google Scholar] [CrossRef] [PubMed]
- Babaei, A.; Asadpour, R.; Mansouri, K.; Sabrivand, A.; Kazemi-Darabadi, S. Lycopene improves testicular damage and sperm quality in experimentally induced varicocele: Relationship with apoptosis, hypoxia, and hyperthermia. Food Sci. Nutr. 2022, 10, 1469–1480. [Google Scholar] [CrossRef] [PubMed]
- Chauvin, T.R.; Griswold, M.D. Characterization of the expression and regulation of genes necessary for myo-inositol biosynthesis and transport in the seminiferous epithelium. Biol. Reprod. 2004, 70, 744–751. [Google Scholar] [CrossRef]
- Cilio, S.; Rienzo, M.; Villano, G.; Mirto, B.F.; Giampaglia, G.; Capone, F.; Ferretti, G.; Di Zazzo, E.; Crocetto, F. Beneficial Effects of Antioxidants in Male Infertility Management: A Narrative Review. Oxygen 2022, 2, 1–11. [Google Scholar] [CrossRef]
- Condorelli, R.A.; La Vignera, S.; Bellanca, S.; Vicari, E.; Calogero, A.E. Myoinositol: Does it improve sperm mitochondrial function and sperm motility? Urology 2012, 79, 1290–1295. [Google Scholar] [CrossRef]
- Governini, L.; Ponchia, R.; Artini, P.G.; Casarosa, E.; Marzi, I.; Capaldo, A.; Luddi, A.; Piomboni, P. Respiratory Mitochondrial Efficiency and DNA Oxidation in Human Sperm after In Vitro Myo-Inositol Treatment. J. Clin. Med. 2020, 9, 1638. [Google Scholar] [CrossRef]
- Calogero, A.E.; Gullo, G.; La Vignera, S.; Condorelli, R.A.; Vaiarelli, A. Myoinositol improves sperm parameters and serum reproductive hormones in patients with idiopathic infertility: A prospective double-blind randomized placebo-controlled study. Andrology 2015, 3, 491–495. [Google Scholar] [CrossRef]
- Vazquez-Levin, M.H.; Veron, G.L. Myo-inositol in health and disease: Its impact on semen parameters and male fertility. Andrology 2020, 8, 277–298. [Google Scholar] [CrossRef]
- Boni, R.; Gallo, A.; Cecchini, S. Kinetic activity, membrane mitochondrial potential, lipid peroxidation, intracellular pH and calcium of frozen/thawed bovine spermatozoa treated with metabolic enhancers. Andrology 2017, 5, 133–145. [Google Scholar] [CrossRef]
- Artini, P.G.; Casarosa, E.; Carletti, E.; Monteleone, P.; Di Noia, A.; Di Berardino, O.M. In vitro effect of myo-inositol on sperm motility in normal and oligoasthenospermia patients undergoing in vitro fertilization. Gynecol. Endocrinol. 2017, 33, 109–112. [Google Scholar] [CrossRef]
- Ibrahim, S.F.; Osman, K.; Das, S.; Othman, A.M.; Majid, N.A.; Rahman, M.P. A study of the antioxidant effect of alpha lipoic acids on sperm quality. Clinics 2008, 63, 545–550. [Google Scholar] [CrossRef]
- Bingham, P.M.; Stuart, S.D.; Zachar, Z. Lipoic acid and lipoic acid analogs in cancer metabolism and chemotherapy. Expert Rev. Clin. Pharmacol. 2014, 7, 837–846. [Google Scholar] [CrossRef] [PubMed]
- Ali, Y.F.; Desouky, O.S.; Selim, N.S.; Ereiba, K.M. Assessment of the role of α-lipoic acid against the oxidative stress of induced iron overload. J. Radiat. Res. Appl. Sci. 2015, 8, 26–35. [Google Scholar] [CrossRef]
- Haghighian, H.K.; Haidari, F.; Mohammadi-Asl, J.; Dadfar, M. Randomized, triple-blind, placebo-controlled clinical trial examining the effects of alpha-lipoic acid supplement on the spermatogram and seminal oxidative stress in infertile men. Fertil. Steril. 2015, 104, 318–324. [Google Scholar] [CrossRef] [PubMed]
- Taherian, S.S.; Khayamabed, R.; Tavalaee, M.; Nasr-Esfahani, M.H. Alpha-lipoic acid minimises reactive oxygen species-induced damages during sperm processing. Andrologia 2019, 51, e13314. [Google Scholar] [CrossRef]
- Di Tucci, C.; Galati, G.; Mattei, G.; Bonanni, V.; Capri, O.; D’Amelio, R.; Muzii, L.; Benedetti Panici, P. The role of alpha lipoic acid in female and male infertility: A systematic review. Gynecol. Endocrinol. 2021, 37, 497–505. [Google Scholar] [CrossRef]
- Barati, E.; Nikzad, H.; Karimian, M. Oxidative stress and male infertility: Current knowledge of pathophysiology and role of antioxidant therapy in disease management. Cell Mol. Life Sci. 2020, 77, 93–113. [Google Scholar] [CrossRef]
- Abbasi, B.; Molavi, N.; Tavalaee, M.; Abbasi, H.; Nasr-Esfahani, M.H. Alpha-lipoic acid improves sperm motility in infertile men after varicocelectomy: A triple-blind randomized controlled trial. Reprod. Biomed. Online 2020, 41, 1084–1091. [Google Scholar] [CrossRef]
- Asa, E.; Ahmadi, R.; Mahmoodi, M.; Mohammadniya, A. Supplementation of freezing media with alpha lipoic acid preserves the structural and functional characteristics of sperm against cryodamage in infertile men with asthenoteratozoospermia. Cryobiology 2020, 96, 166–174. [Google Scholar] [CrossRef]
- Walke, G.; Gaurkar, S.S.; Prasad, R.; Lohakare, T.; Wanjari, M. The Impact of Oxidative Stress on Male Reproductive Function: Exploring the Role of Antioxidant Supplementation. Cureus 2023, 15, e42583. [Google Scholar] [CrossRef]
- Schisterman, E.F.; Sjaarda, L.A.; Clemons, T.; Carrell, D.T.; Perkins, N.J.; Johnstone, E.; Lamb, D.; Chaney, K.; Van Voorhis, B.J.; Ryan, G.; et al. Effect of Folic Acid and Zinc Supplementation in Men on Semen Quality and Live Birth Among Couples Undergoing Infertility Treatment: A Randomized Clinical Trial. JAMA 2020, 323, 35–48. [Google Scholar] [CrossRef]
- Henkel, R.; Sandhu, I.S.; Agarwal, A. The excessive use of antioxidant therapy: A possible cause of male infertility? Andrologia 2019, 51, e13162. [Google Scholar] [CrossRef]
- Halliwell, B. The antioxidant paradox. Lancet 2000, 355, 1179–1180. [Google Scholar] [CrossRef] [PubMed]
- Castagne, V.; Lefevre, K.; Natero, R.; Clarke, P.G.; Bedker, D.A. An optimal redox status for the survival of axotomized ganglion cells in the developing retina. Neuroscience 1999, 93, 313–320. [Google Scholar] [CrossRef] [PubMed]
- Zhang, X.; Min, X.; Li, C.; Benjamin, I.J.; Qian, B.; Zhang, X.; Ding, Z.; Gao, X.; Yao, Y.; Ma, Y.; et al. Involvement of reductive stress in the cardiomyopathy in transgenic mice with cardiac-specific overexpression of heat shock protein 27. Hypertension 2010, 55, 1412–1417. [Google Scholar] [CrossRef]
- Rajasekaran, N.S.; Connell, P.; Christians, E.S.; Yan, L.J.; Taylor, R.P.; Orosz, A.; Zhang, X.Q.; Stevenson, T.J.; Peshock, R.M.; Leopold, J.A.; et al. Human alpha B-crystallin mutation causes oxido-reductive stress and protein aggregation cardiomyopathy in mice. Cell 2007, 130, 427–439. [Google Scholar] [CrossRef] [PubMed]
- Mentor, S.; Fisher, D. Aggressive Antioxidant Reductive Stress Impairs Brain Endothelial Cell Angiogenesis and Blood Brain Barrier Function. Curr. Neurovasc. Res. 2017, 14, 71–81. [Google Scholar] [CrossRef]
- Fisher, D.; Mentor, S. Antioxidant-induced reductive stress has untoward consequences on the brain microvasculature. Neural Regen. Res. 2017, 12, 743–744. [Google Scholar] [CrossRef]
- Lamosova, D.; Jurani, M.; Greksak, M.; Nakano, M.; Vanekova, M. Effect of Rooibos tea (Aspalathus linearis) on chick skeletal muscle cell growth in culture. Comp. Biochem. Physiol. C Pharmacol. Toxicol. Endocrinol. 1997, 116, 39–45. [Google Scholar] [CrossRef] [PubMed]
- Singh, F.; Charles, A.L.; Schlagowski, A.I.; Bouitbir, J.; Bonifacio, A.; Piquard, F.; Krahenbuhl, S.; Geny, B.; Zoll, J. Reductive stress impairs myoblasts mitochondrial function and triggers mitochondrial hormesis. Biochim. Biophys. Acta 2015, 1853, 1574–1585. [Google Scholar] [CrossRef]
- Capece, M.; Romeo, G.; Ruffo, A.; Romis, L.; Mordente, S.; Di Lauro, G. A phytotherapic approach to reduce sperm DNA fragmentation in patients with male infertility. Urologia 2017, 84, 79–82. [Google Scholar] [CrossRef]
- Aoun, A.; Khoury, V.E.; Malakieh, R. Can Nutrition Help in the Treatment of Infertility? Prev. Nutr. Food Sci. 2021, 26, 109–120. [Google Scholar] [CrossRef] [PubMed]
- Terai, K.; Horie, S.; Fukuhara, S.; Miyagawa, Y.; Kobayashi, K.; Tsujimura, A. Combination therapy with antioxidants improves total motile sperm counts: A Preliminary Study. Reprod. Med. Biol. 2020, 19, 89–94. [Google Scholar] [CrossRef]
- Bisht, S.; Faiq, M.; Tolahunase, M.; Dada, R. Oxidative stress and male infertility. Nat. Rev. Urol. 2017, 14, 470–485. [Google Scholar] [CrossRef] [PubMed]
- Santoro, M.; Aquila, S.; Russo, G. Sperm performance in oligoasthenoteratozoospermic patients is induced by a nutraceuticals mix, containing mainly myo-inositol. Syst. Biol. Reprod. Med. 2021, 67, 50–63. [Google Scholar] [CrossRef]
- Scaruffi, P.; Licata, E.; Maccarini, E.; Massarotti, C.; Bovis, F.; Sozzi, F.; Stigliani, S.; Dal Lago, A.; Casciano, I.; Rago, R.; et al. Oral Antioxidant Treatment of Men Significantly Improves the Reproductive Outcome of IVF Cycles. J. Clin. Med. 2021, 10, 3254. [Google Scholar] [CrossRef]
- Steiner, A.Z.; Hansen, K.R.; Barnhart, K.T.; Cedars, M.I.; Legro, R.S.; Diamond, M.P.; Krawetz, S.A.; Usadi, R.; Baker, V.L.; Coward, R.M.; et al. The effect of antioxidants on male factor infertility: The Males, Antioxidants, and Infertility (MOXI) randomized clinical trial. Fertil. Steril. 2020, 113, 552–560 e553. [Google Scholar] [CrossRef]
- Salas-Huetos, A.; James, E.R.; Aston, K.I.; Jenkins, T.G.; Carrell, D.T. Diet and sperm quality: Nutrients, foods and dietary patterns. Reprod. Biol. 2019, 19, 219–224. [Google Scholar] [CrossRef]
- Salas-Huetos, A.; Bullo, M.; Salas-Salvado, J. Dietary patterns, foods and nutrients in male fertility parameters and fecundability: A systematic review of observational studies. Hum. Reprod. Update 2017, 23, 371–389. [Google Scholar] [CrossRef] [PubMed]
- Ozer, C. Antioxidant treatment of increased sperm DNA fragmentation: Complex combinations are not more successful. Arch Ital. Urol. Androl. 2020, 92. [Google Scholar] [CrossRef]
- Sidorkiewicz, I.; Zareba, K.; Wolczynski, S.; Czerniecki, J. Endocrine-disrupting chemicals-Mechanisms of action on male reproductive system. Toxicol. Ind. Health 2017, 33, 601–609. [Google Scholar] [CrossRef]
- Agarwal, A.; Allamaneni, S.S.; Nallella, K.P.; George, A.T.; Mascha, E. Correlation of reactive oxygen species levels with the fertilization rate after in vitro fertilization: A qualified meta-analysis. Fertil. Steril. 2005, 84, 228–231. [Google Scholar] [CrossRef]
- de Ligny, W.; Smits, R.M.; Mackenzie-Proctor, R.; Jordan, V.; Fleischer, K.; de Bruin, J.P.; Showell, M.G. Antioxidants for male subfertility. Cochrane Database Syst. Rev. 2022, 5, CD007411. [Google Scholar] [CrossRef]
- Hamada, A.; Esteves, S.C.; Nizza, M.; Agarwal, A. Unexplained male infertility: Diagnosis and management. Int. Braz. J. Urol. 2012, 38, 576–594. [Google Scholar] [CrossRef] [PubMed]
- Aitken, R.J. The Male Is Significantly Implicated as the Cause of Unexplained Infertility. Semin. Reprod. Med. 2020, 38, 3–20. [Google Scholar] [CrossRef] [PubMed]
- Ko, E.Y.; Sabanegh, E.S., Jr.; Agarwal, A. Male infertility testing: Reactive oxygen species and antioxidant capacity. Fertil. Steril. 2014, 102, 1518–1527. [Google Scholar] [CrossRef] [PubMed]
- Wagner, H.; Cheng, J.W.; Ko, E.Y. Role of reactive oxygen species in male infertility: An updated review of literature. Arab J. Urol. 2018, 16, 35–43. [Google Scholar] [CrossRef]
- Imamovic Kumalic, S.; Pinter, B. Review of clinical trials on effects of oral antioxidants on basic semen and other parameters in idiopathic oligoasthenoteratozoospermia. Biomed. Res. Int. 2014, 2014, 426951. [Google Scholar] [CrossRef]
- Arafa, M.; Agarwal, A.; Majzoub, A.; Panner Selvam, M.K.; Baskaran, S.; Henkel, R.; Elbardisi, H. Efficacy of Antioxidant Supplementation on Conventional and Advanced Sperm Function Tests in Patients with Idiopathic Male Infertility. Antioxidants 2020, 9, 219. [Google Scholar] [CrossRef] [PubMed]
- Showell, M.G.; Mackenzie-Proctor, R.; Brown, J.; Yazdani, A.; Stankiewicz, M.T.; Hart, R.J. Antioxidants for male subfertility. Cochrane Database Syst. Rev. 2014, 12, CD007411. [Google Scholar] [CrossRef]
- Smits, R.M.; Mackenzie-Proctor, R.; Yazdani, A.; Stankiewicz, M.T.; Jordan, V.; Showell, M.G. Antioxidants for male subfertility. Cochrane Database Syst. Rev. 2019, 3, CD007411. [Google Scholar] [CrossRef] [PubMed]
- Agarwal, A.; Leisegang, K.; Majzoub, A.; Henkel, R.; Finelli, R.; Panner Selvam, M.K.; Tadros, N.; Parekh, N.; Ko, E.Y.; Cho, C.L.; et al. Utility of Antioxidants in the Treatment of Male Infertility: Clinical Guidelines Based on a Systematic Review and Analysis of Evidence. World J. Mens Health 2021, 39, 233–290. [Google Scholar] [CrossRef]
- Agarwal, A.; Esteves, S.C. Varicocele and male infertility: Current concepts and future perspectives. Asian J. Androl. 2016, 18, 161–162. [Google Scholar] [CrossRef]
- Abd-Elmoaty, M.A.; Saleh, R.; Sharma, R.; Agarwal, A. Increased levels of oxidants and reduced antioxidants in semen of infertile men with varicocele. Fertil. Steril. 2010, 94, 1531–1534. [Google Scholar] [CrossRef] [PubMed]
- Agarwal, A.; Hamada, A.; Esteves, S.C. Insight into oxidative stress in varicocele-associated male infertility: Part 1. Nat. Rev. Urol. 2012, 9, 678–690. [Google Scholar] [CrossRef]
- Mehraban, D.; Ansari, M.; Keyhan, H.; Sedighi Gilani, M.; Naderi, G.; Esfehani, F. Comparison of nitric oxide concentration in seminal fluid between infertile patients with and without varicocele and normal fertile men. Urol. J. 2005, 2, 106–110. [Google Scholar] [PubMed]
- Mostafa, T.; Anis, T.; El Nashar, A.; Imam, H.; Osman, I. Seminal plasma reactive oxygen species-antioxidants relationship with varicocele grade. Andrologia 2012, 44, 66–69. [Google Scholar] [CrossRef]
- Mostafa, T.; Anis, T.; Imam, H.; El-Nashar, A.R.; Osman, I.A. Seminal reactive oxygen species-antioxidant relationship in fertile males with and without varicocele. Andrologia 2009, 41, 125–129. [Google Scholar] [CrossRef] [PubMed]
- Sofikitis, N.; Stavrou, S.; Skouros, S.; Dimitriadis, F.; Tsounapi, P.; Takenaka, A. Mysteries, Facts, and Fiction in Varicocele Pathophysiology and Treatment. Eur. Urol. Suppl. 2014, 13, 89–99. [Google Scholar] [CrossRef]
- Kaltsas, A.; Markou, E.; Zachariou, A.; Dimitriadis, F.; Mamoulakis, C.; Andreadakis, S.; Giannakis, I.; Tsounapi, P.; Takenaka, A.; Sofikitis, N. Varicoceles in Men With Non-obstructive Azoospermia: The Dilemma to Operate or Not. Front. Reprod. Health 2022, 4, 811487. [Google Scholar] [CrossRef] [PubMed]
- Wang, J.; Wang, T.; Ding, W.; Wu, J.; Wu, G.; Wang, Y.; Zhou, Z.; Xu, L.; Cui, Y. Efficacy of antioxidant therapy on sperm quality measurements after varicocelectomy: A systematic review and meta-analysis. Andrologia 2019, 51, e13396. [Google Scholar] [CrossRef] [PubMed]
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Kaltsas, A. Oxidative Stress and Male Infertility: The Protective Role of Antioxidants. Medicina 2023, 59, 1769. https://doi.org/10.3390/medicina59101769
Kaltsas A. Oxidative Stress and Male Infertility: The Protective Role of Antioxidants. Medicina. 2023; 59(10):1769. https://doi.org/10.3390/medicina59101769
Chicago/Turabian StyleKaltsas, Aris. 2023. "Oxidative Stress and Male Infertility: The Protective Role of Antioxidants" Medicina 59, no. 10: 1769. https://doi.org/10.3390/medicina59101769