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Unbalanced Expression of Glutathione Peroxidase 4 and Arachidonate 15-Lipoxygenase Affects Acrosome Reaction and In Vitro Fertilization
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 characteri...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9456195/ https://www.ncbi.nlm.nih.gov/pubmed/36077303 http://dx.doi.org/10.3390/ijms23179907 |
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author | Soria-Tiedemann, Mariana Michel, Geert Urban, Iris Aldrovandi, Maceler O’Donnell, Valerie B. Stehling, Sabine Kuhn, Hartmut Borchert, Astrid |
author_facet | Soria-Tiedemann, Mariana Michel, Geert Urban, Iris Aldrovandi, Maceler O’Donnell, Valerie B. Stehling, Sabine Kuhn, Hartmut Borchert, Astrid |
author_sort | Soria-Tiedemann, Mariana |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-9456195 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-94561952022-09-09 Unbalanced Expression of Glutathione Peroxidase 4 and Arachidonate 15-Lipoxygenase Affects Acrosome Reaction and In Vitro Fertilization Soria-Tiedemann, Mariana Michel, Geert Urban, Iris Aldrovandi, Maceler O’Donnell, Valerie B. Stehling, Sabine Kuhn, Hartmut Borchert, Astrid Int J Mol Sci Article 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. MDPI 2022-08-31 /pmc/articles/PMC9456195/ /pubmed/36077303 http://dx.doi.org/10.3390/ijms23179907 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Soria-Tiedemann, Mariana Michel, Geert Urban, Iris Aldrovandi, Maceler O’Donnell, Valerie B. Stehling, Sabine Kuhn, Hartmut Borchert, Astrid Unbalanced Expression of Glutathione Peroxidase 4 and Arachidonate 15-Lipoxygenase Affects Acrosome Reaction and In Vitro Fertilization |
title | Unbalanced Expression of Glutathione Peroxidase 4 and Arachidonate 15-Lipoxygenase Affects Acrosome Reaction and In Vitro Fertilization |
title_full | Unbalanced Expression of Glutathione Peroxidase 4 and Arachidonate 15-Lipoxygenase Affects Acrosome Reaction and In Vitro Fertilization |
title_fullStr | Unbalanced Expression of Glutathione Peroxidase 4 and Arachidonate 15-Lipoxygenase Affects Acrosome Reaction and In Vitro Fertilization |
title_full_unstemmed | Unbalanced Expression of Glutathione Peroxidase 4 and Arachidonate 15-Lipoxygenase Affects Acrosome Reaction and In Vitro Fertilization |
title_short | Unbalanced Expression of Glutathione Peroxidase 4 and Arachidonate 15-Lipoxygenase Affects Acrosome Reaction and In Vitro Fertilization |
title_sort | unbalanced expression of glutathione peroxidase 4 and arachidonate 15-lipoxygenase affects acrosome reaction and in vitro fertilization |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9456195/ https://www.ncbi.nlm.nih.gov/pubmed/36077303 http://dx.doi.org/10.3390/ijms23179907 |
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