{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T04:11:32Z","timestamp":1782965492765,"version":"3.54.5"},"reference-count":88,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2022,8,31]],"date-time":"2022-08-31T00:00:00Z","timestamp":1661904000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["Ku 961\/13-1"],"award-info":[{"award-number":["Ku 961\/13-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["Ku 961\/14-1"],"award-info":[{"award-number":["Ku 961\/14-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Charit\u00e9-Universit\u00e4tsmedizin Berlin","award":["Ku 961\/13-1"],"award-info":[{"award-number":["Ku 961\/13-1"]}]},{"name":"Charit\u00e9-Universit\u00e4tsmedizin Berlin","award":["Ku 961\/14-1"],"award-info":[{"award-number":["Ku 961\/14-1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Glutathione peroxidase 4 (Gpx4) and arachidonic acid 15 lipoxygenase (Alox15) are counterplayers in oxidative lipid metabolism and both enzymes have been implicated in spermatogenesis. However, the roles of the two proteins in acrosomal exocytosis have not been explored in detail. Here we characterized Gpx4 distribution in mouse sperm and detected the enzyme not only in the midpiece of the resting sperm but also at the anterior region of the head, where the acrosome is localized. During sperm capacitation, Gpx4 translocated to the post-acrosomal compartment. Sperm from Gpx4+\/Sec46Ala mice heterozygously expressing a catalytically silent enzyme displayed an increased expression of phosphotyrosyl proteins, impaired acrosomal exocytosis after in vitro capacitation and were not suitable for in vitro fertilization. Alox15-deficient sperm showed normal acrosome reactions but when crossed into a Gpx4-deficient background spontaneous acrosomal exocytosis was observed during capacitation and these cells were even less suitable for in vitro fertilization. Taken together, our data indicate that heterozygous expression of a catalytically silent Gpx4 variant impairs acrosomal exocytosis and in vitro fertilization. Alox15 deficiency hardly impacted the acrosome reaction but when crossed into the Gpx4-deficient background spontaneous acrosomal exocytosis was induced. The detailed molecular mechanisms for the observed effects may be related to the compromised redox homeostasis.<\/jats:p>","DOI":"10.3390\/ijms23179907","type":"journal-article","created":{"date-parts":[[2022,9,1]],"date-time":"2022-09-01T01:50:51Z","timestamp":1661997051000},"page":"9907","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Unbalanced Expression of Glutathione Peroxidase 4 and Arachidonate 15-Lipoxygenase Affects Acrosome Reaction and In Vitro Fertilization"],"prefix":"10.3390","volume":"23","author":[{"given":"Mariana","family":"Soria-Tiedemann","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Charit\u00e9platz 1, D-10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geert","family":"Michel","sequence":"additional","affiliation":[{"name":"Department of Transgenic Technologies, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Lindenberger Weg 80, D-13125 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iris","family":"Urban","sequence":"additional","affiliation":[{"name":"Department of Transgenic Technologies, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Lindenberger Weg 80, D-13125 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maceler","family":"Aldrovandi","sequence":"additional","affiliation":[{"name":"Systems Immunity Research Institute, School of Medicine, Cardiff University, Cardiff CF14 4XN, UK"},{"name":"Helmholtz Zentrum M\u00fcnchen, Institute of Metabolism and Cell Death, Ingolst\u00e4dter Landstr. 1, D-85764 Neuherberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valerie","family":"O\u2019Donnell","sequence":"additional","affiliation":[{"name":"Systems Immunity Research Institute, School of Medicine, Cardiff University, Cardiff CF14 4XN, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabine","family":"Stehling","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Charit\u00e9platz 1, D-10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8142-3192","authenticated-orcid":false,"given":"Hartmut","family":"Kuhn","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Charit\u00e9platz 1, D-10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Astrid","family":"Borchert","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Charit\u00e9platz 1, D-10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"dev176966","DOI":"10.1242\/dev.176966","article-title":"The molecular mechanisms mediating mammalian fertilization","volume":"146","author":"Bhakta","year":"2019","journal-title":"Development"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"341","DOI":"10.3389\/fcell.2019.00341","article-title":"Signaling Enzymes Required for Sperm Maturation and Fertilization in Mammals","volume":"7","author":"Dey","year":"2019","journal-title":"Front. 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