{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T15:21:13Z","timestamp":1790349673413,"version":"4.1.0"},"reference-count":58,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2020,12,31]],"date-time":"2020-12-31T00:00:00Z","timestamp":1609372800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP1163319"],"award-info":[{"award-number":["APP1163319"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>A prevalent cause of sperm dysfunction in male infertility patients is the overproduction of reactive oxygen species, an attendant increase in lipid peroxidation and the production of cytotoxic reactive carbonyl species such as 4-hydroxynonenal. Our previous studies have implicated arachidonate 15-lipoxygenase (ALOX15) in the production of 4-hydroxynonenal in developing germ cells. Here, we have aimed to develop a further mechanistic understanding of the lipoxygenase-lipid peroxidation pathway in human spermatozoa. Through pharmacological inhibition studies, we identified a protective role for phospholipase enzymes in the liberation of peroxidised polyunsaturated fatty acids from the human sperm membrane. Our results also revealed that arachidonic acid, linoleic acid and docosahexanoic acid are key polyunsaturated fatty acid substrates for ALOX15. Upon examination of ALOX15 in the spermatozoa of infertile patients compared to their normozoospermic counterparts, we observed significantly elevated levels of ALOX15 protein abundance in the infertile population and an increase in 4-hydroxynonenal adducts. Collectively, these data confirm the involvement of ALOX15 in the oxidative stress cascade of human spermatozoa and support the notion that increased ALOX15 abundance in sperm cells may accentuate membrane lipid peroxidation and cellular dysfunction, ultimately contributing to male infertility.<\/jats:p>","DOI":"10.3390\/antiox10010043","type":"journal-article","created":{"date-parts":[[2020,12,31]],"date-time":"2020-12-31T14:31:49Z","timestamp":1609425109000},"page":"43","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Mechanistic Insight into the Regulation of Lipoxygenase-Driven Lipid Peroxidation Events in Human Spermatozoa and Their Impact on Male Fertility"],"prefix":"10.3390","volume":"10","author":[{"given":"Jessica L. H.","family":"Walters","sequence":"first","affiliation":[{"name":"Priority Research Centre for Reproductive Science, Schools of Biomedical Science &amp; Pharmacy and Environmental &amp; Life Sciences, The University of Newcastle, Callaghan, NSW 2308, Australia"},{"name":"Hunter Medical Research Institute, Pregnancy and Reproduction Program, New Lambton Heights, NSW 2305, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda L.","family":"Anderson","sequence":"additional","affiliation":[{"name":"Priority Research Centre for Reproductive Science, Schools of Biomedical Science &amp; Pharmacy and Environmental &amp; Life Sciences, The University of Newcastle, Callaghan, NSW 2308, Australia"},{"name":"Hunter Medical Research Institute, Pregnancy and Reproduction Program, New Lambton Heights, NSW 2305, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah J.","family":"Martins da Silva","sequence":"additional","affiliation":[{"name":"Reproductive Medicine Research Group, School of Medicine, University of Dundee, Dundee DD1 9SY, UK"},{"name":"Assisted Conception Unit, Ninewells Hospital and Medical School, Dundee DD1 9SY, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. John","family":"Aitken","sequence":"additional","affiliation":[{"name":"Priority Research Centre for Reproductive Science, Schools of Biomedical Science &amp; Pharmacy and Environmental &amp; Life Sciences, The University of Newcastle, Callaghan, NSW 2308, Australia"},{"name":"Hunter Medical Research Institute, Pregnancy and Reproduction Program, New Lambton Heights, NSW 2305, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6978-6123","authenticated-orcid":false,"given":"Geoffry N.","family":"De Iuliis","sequence":"additional","affiliation":[{"name":"Priority Research Centre for Reproductive Science, Schools of Biomedical Science &amp; Pharmacy and Environmental &amp; Life Sciences, The University of Newcastle, Callaghan, NSW 2308, Australia"},{"name":"Hunter Medical Research Institute, Pregnancy and Reproduction Program, New Lambton Heights, NSW 2305, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9672-2371","authenticated-orcid":false,"given":"Jessie M.","family":"Sutherland","sequence":"additional","affiliation":[{"name":"Priority Research Centre for Reproductive Science, Schools of Biomedical Science &amp; Pharmacy and Environmental &amp; Life Sciences, The University of Newcastle, Callaghan, NSW 2308, Australia"},{"name":"Hunter Medical Research Institute, Pregnancy and Reproduction Program, New Lambton Heights, NSW 2305, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2745-8188","authenticated-orcid":false,"given":"Brett","family":"Nixon","sequence":"additional","affiliation":[{"name":"Priority Research Centre for Reproductive Science, Schools of Biomedical Science &amp; Pharmacy and Environmental &amp; Life Sciences, The University of Newcastle, Callaghan, NSW 2308, Australia"},{"name":"Hunter Medical Research Institute, Pregnancy and Reproduction Program, New Lambton Heights, NSW 2305, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7256-1403","authenticated-orcid":false,"given":"Elizabeth G.","family":"Bromfield","sequence":"additional","affiliation":[{"name":"Priority Research Centre for Reproductive Science, Schools of Biomedical Science &amp; Pharmacy and Environmental &amp; Life Sciences, The University of Newcastle, Callaghan, NSW 2308, Australia"},{"name":"Hunter Medical Research Institute, Pregnancy and Reproduction Program, New Lambton Heights, NSW 2305, Australia"},{"name":"Discipline of Biochemistry and Cell Biology, Faculty of Veterinary Medicine, Utrecht University, 3584 CM Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1093\/humupd\/dmx021","article-title":"The diagnosis of male infertility: An analysis of the evidence to support the development of global WHO guidance\u2014challenges and future research opportunities","volume":"23","author":"Barratt","year":"2017","journal-title":"Hum. 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