{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T03:57:04Z","timestamp":1791863824583,"version":"4.3.4"},"reference-count":195,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,4,25]],"date-time":"2026-04-25T00:00:00Z","timestamp":1777075200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Oxidative stress is one of the few defined causes of male infertility affecting at least one third of patients attending infertility clinics. Human spermatozoa are vulnerable to this form of attack because their stripped-down architecture means that they possess limited antioxidant protection and little capacity for biochemical repair. They also compound their vulnerability by being active generators of reactive oxygen species (ROS) and possessing multiple substrates for oxidative damage. The major sources of ROS in these cells are their mitochondria, an L-amino acid oxidase (IL4I1) and a calcium-dependent NADPH oxidase (NOX5). Spermatozoa tolerate the risks associated with ROS generation because their biology is heavily dependent on redox regulation. ROS are important mediators of sperm capacitation, stimulating the generation of cAMP and prostaglandins, inhibiting protein phosphatases and encouraging removal of cholesterol from the plasma membrane. Furthermore, during fertilization, the ability of ROS to activate metalloproteinases facilitates penetration of the zona pellucida and sperm\u2013oocyte fusion. While ROS are physiologically important for sperm function, the over-production of these metabolites can impair sperm function. Antioxidants have therefore assumed some importance as a possible therapy for the infertile male. However, before this potential can be realized, we need to optimize the composition and dose of reagents used in such formulations and develop improved methods of diagnosing oxidative stress within the patient population.<\/jats:p>","DOI":"10.3390\/ijms27093819","type":"journal-article","created":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T11:33:37Z","timestamp":1777376017000},"page":"3819","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Molecular Advances in Male Infertility and Fertility: Importance of Redox Regulation and Oxidative Stress"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9152-156X","authenticated-orcid":false,"given":"Robert J.","family":"Aitken","sequence":"first","affiliation":[{"name":"Centre for Reproductive Science, School of Science, University of Newcastle, Callaghan, NSW 2308, Australia"},{"name":"Hunter Medical Research Institute, New Lambton Heights, Newcastle, NSW 2305, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4463-6532","authenticated-orcid":false,"given":"Monica H.","family":"Vazquez-Levin","sequence":"additional","affiliation":[{"name":"Institute of Biology and Experimental Medicine (IBYME), Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas, Buenos Aires C1428ADN, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jo\u00e3o S.","family":"Hallak","sequence":"additional","affiliation":[{"name":"Centro Universit\u00e1rio em Sa\u00fade, Faculdade de Medicina do ABC, Santo Andr\u00e9 09060-060, SP, Brazil"},{"name":"Instituto ANDROSCIENCE, de Ci\u00eancia, Educa\u00e7\u00e3o e Projetos Avan\u00e7ados em Sa\u00fade Masculina, S\u00e3o Paulo 04000-000, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6598-2442","authenticated-orcid":false,"given":"Thiago A.","family":"Teixeira","sequence":"additional","affiliation":[{"name":"Instituto ANDROSCIENCE, de Ci\u00eancia, Educa\u00e7\u00e3o e Projetos Avan\u00e7ados em Sa\u00fade Masculina, S\u00e3o Paulo 04000-000, SP, Brazil"},{"name":"Disciplina de Urologia, Departamento de Cirurgia, Faculdade de Medicina, Universidade Federal do Amap\u00e1\u2013UNIFAP, Macap\u00e1 66600-000, AP, Brazil"},{"name":"Grupo de Estudos em Sa\u00fade Masculina, Instituto de Estudos Avan\u00e7ados, Universidade de S\u00e3o Paulo\u2013IEA-USP, S\u00e3o Paulo 01230-000, SP, Brazil"},{"name":"ANDROSCIENCE, Centro de Ci\u00eancia e Inova\u00e7\u00e3o em Andrologia, Laborat\u00f3rio Cl\u00ednico e de Pesquisa de Alta Complexidade, S\u00e3o Paulo 01310-000, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge","family":"Hallak","sequence":"additional","affiliation":[{"name":"Instituto ANDROSCIENCE, de Ci\u00eancia, Educa\u00e7\u00e3o e Projetos Avan\u00e7ados em Sa\u00fade Masculina, S\u00e3o Paulo 04000-000, SP, Brazil"},{"name":"Grupo de Estudos em Sa\u00fade Masculina, Instituto de Estudos Avan\u00e7ados, Universidade de S\u00e3o Paulo\u2013IEA-USP, S\u00e3o Paulo 01230-000, SP, Brazil"},{"name":"ANDROSCIENCE, Centro de Ci\u00eancia e Inova\u00e7\u00e3o em Andrologia, Laborat\u00f3rio Cl\u00ednico e de Pesquisa de Alta Complexidade, S\u00e3o Paulo 01310-000, SP, Brazil"},{"name":"Departamento de Patologia, Unidade de Toxicologia Reprodutiva, Faculdade de Medicina da Universidade de S\u00e3o Paulo\u2013FMUSP, S\u00e3o Paulo 01246-000, SP, Brazil"},{"name":"Disciplina de Urologia, Departamento de Cirurgia, Hospital das Cl\u00ednicas da Faculdade de Medicina da Universidade de S\u00e3o Paulo\u2013FMUSP, S\u00e3o Paulo 01246-000, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1016\/j.fertnstert.2025.10.017","article-title":"Evidence that declining human fecundity contributes to the fertility crisis","volume":"125","author":"Beck","year":"2026","journal-title":"Fertil. 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