Protamine-2 Deficiency Initiates a Reactive Oxygen Species (ROS)-Mediated Destruction Cascade during Epididymal Sperm Maturation in Mice
Protamines are the safeguards of the paternal sperm genome. They replace most of the histones during spermiogenesis, resulting in DNA hypercondensation, thereby protecting its genome from environmental noxa. Impaired protamination has been linked to male infertility in mice and humans in many studie...
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MDPI AG
2020-07-01
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| Online Access: | https://www.mdpi.com/2073-4409/9/8/1789 |
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| author | Simon Schneider Farhad Shakeri Christian Trötschel Lena Arévalo Alexander Kruse Andreas Buness Ansgar Poetsch Klaus Steger Hubert Schorle |
| author_facet | Simon Schneider Farhad Shakeri Christian Trötschel Lena Arévalo Alexander Kruse Andreas Buness Ansgar Poetsch Klaus Steger Hubert Schorle |
| author_sort | Simon Schneider |
| collection | DOAJ |
| description | Protamines are the safeguards of the paternal sperm genome. They replace most of the histones during spermiogenesis, resulting in DNA hypercondensation, thereby protecting its genome from environmental noxa. Impaired protamination has been linked to male infertility in mice and humans in many studies. Apart from impaired DNA integrity, protamine-deficient human and murine sperm show multiple secondary effects, including decreased motility and aberrant head morphology. In this study, we use a Protamine<i>-2</i> (<i>Prm2</i>)-deficient mouse model in combination with label-free quantitative proteomics to decipher the underlying molecular processes of these effects. We show that loss of the sperm’s antioxidant capacity, indicated by downregulation of key proteins like Superoxide dismutase type 1 (SOD1) and Peroxiredoxin 5 (PRDX5), ultimately initiates an oxidative stress-mediated destruction cascade during epididymal sperm maturation. This is confirmed by an increased level of 8-OHdG in epididymal sperm, a biomarker for oxidative stress-mediated DNA damage. <i>Prm2</i>-deficient testicular sperm are not affected and initiate the proper development of blastocyst stage preimplantation embryos in vitro upon intracytoplasmic sperm injection (ICSI) into oocytes. Our results provide new insight into the role of <i>Prm2</i> and its downstream molecular effects on sperm function and present an important contribution to the investigation of new treatment regimens for infertile men with impaired protamination. |
| first_indexed | 2024-03-10T18:11:02Z |
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| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T18:11:02Z |
| publishDate | 2020-07-01 |
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| series | Cells |
| spelling | doaj.art-5652533a90f64a1eac9e22a61d7334662023-11-20T08:07:08ZengMDPI AGCells2073-44092020-07-0198178910.3390/cells9081789Protamine-2 Deficiency Initiates a Reactive Oxygen Species (ROS)-Mediated Destruction Cascade during Epididymal Sperm Maturation in MiceSimon Schneider0Farhad Shakeri1Christian Trötschel2Lena Arévalo3Alexander Kruse4Andreas Buness5Ansgar Poetsch6Klaus Steger7Hubert Schorle8Department of Developmental Pathology, Institute of Pathology, University Hospital Bonn, 53127 Bonn, GermanyInstitute for Medical Biometry, Informatics and Epidemiology, Medical Faculty, University of Bonn, 53127 Bonn, GermanyDepartment of Plant Biochemistry, Ruhr-University Bochum, 44801 Bochum, GermanyDepartment of Developmental Pathology, Institute of Pathology, University Hospital Bonn, 53127 Bonn, GermanyDepartment of Urology, Pediatric Urology and Andrology, Section Molecular Andrology, Biomedical Research Center of the Justus-Liebig University Gießen, 35392 Gießen, GermanyInstitute for Medical Biometry, Informatics and Epidemiology, Medical Faculty, University of Bonn, 53127 Bonn, GermanyDepartment of Plant Biochemistry, Ruhr-University Bochum, 44801 Bochum, GermanyDepartment of Urology, Pediatric Urology and Andrology, Section Molecular Andrology, Biomedical Research Center of the Justus-Liebig University Gießen, 35392 Gießen, GermanyDepartment of Developmental Pathology, Institute of Pathology, University Hospital Bonn, 53127 Bonn, GermanyProtamines are the safeguards of the paternal sperm genome. They replace most of the histones during spermiogenesis, resulting in DNA hypercondensation, thereby protecting its genome from environmental noxa. Impaired protamination has been linked to male infertility in mice and humans in many studies. Apart from impaired DNA integrity, protamine-deficient human and murine sperm show multiple secondary effects, including decreased motility and aberrant head morphology. In this study, we use a Protamine<i>-2</i> (<i>Prm2</i>)-deficient mouse model in combination with label-free quantitative proteomics to decipher the underlying molecular processes of these effects. We show that loss of the sperm’s antioxidant capacity, indicated by downregulation of key proteins like Superoxide dismutase type 1 (SOD1) and Peroxiredoxin 5 (PRDX5), ultimately initiates an oxidative stress-mediated destruction cascade during epididymal sperm maturation. This is confirmed by an increased level of 8-OHdG in epididymal sperm, a biomarker for oxidative stress-mediated DNA damage. <i>Prm2</i>-deficient testicular sperm are not affected and initiate the proper development of blastocyst stage preimplantation embryos in vitro upon intracytoplasmic sperm injection (ICSI) into oocytes. Our results provide new insight into the role of <i>Prm2</i> and its downstream molecular effects on sperm function and present an important contribution to the investigation of new treatment regimens for infertile men with impaired protamination.https://www.mdpi.com/2073-4409/9/8/1789protaminessperminfertilityROS |
| spellingShingle | Simon Schneider Farhad Shakeri Christian Trötschel Lena Arévalo Alexander Kruse Andreas Buness Ansgar Poetsch Klaus Steger Hubert Schorle Protamine-2 Deficiency Initiates a Reactive Oxygen Species (ROS)-Mediated Destruction Cascade during Epididymal Sperm Maturation in Mice Cells protamines sperm infertility ROS |
| title | Protamine-2 Deficiency Initiates a Reactive Oxygen Species (ROS)-Mediated Destruction Cascade during Epididymal Sperm Maturation in Mice |
| title_full | Protamine-2 Deficiency Initiates a Reactive Oxygen Species (ROS)-Mediated Destruction Cascade during Epididymal Sperm Maturation in Mice |
| title_fullStr | Protamine-2 Deficiency Initiates a Reactive Oxygen Species (ROS)-Mediated Destruction Cascade during Epididymal Sperm Maturation in Mice |
| title_full_unstemmed | Protamine-2 Deficiency Initiates a Reactive Oxygen Species (ROS)-Mediated Destruction Cascade during Epididymal Sperm Maturation in Mice |
| title_short | Protamine-2 Deficiency Initiates a Reactive Oxygen Species (ROS)-Mediated Destruction Cascade during Epididymal Sperm Maturation in Mice |
| title_sort | protamine 2 deficiency initiates a reactive oxygen species ros mediated destruction cascade during epididymal sperm maturation in mice |
| topic | protamines sperm infertility ROS |
| url | https://www.mdpi.com/2073-4409/9/8/1789 |
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