Oligogenic heterozygous inheritance of sperm abnormalities in mouse
Male infertility is an important health concern that is expected to have a major genetic etiology. Although high-throughput sequencing has linked gene defects to more than 50% of rare and severe sperm anomalies, less than 20% of common and moderate forms are explained. We hypothesized that this low...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2022-04-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/75373 |
| _version_ | 1828374827748032512 |
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| author | Guillaume Martinez Charles Coutton Corinne Loeuillet Caroline Cazin Jana Muroňová Magalie Boguenet Emeline Lambert Magali Dhellemmes Geneviève Chevalier Jean-Pascal Hograindleur Charline Vilpreux Yasmine Neirijnck Zine-Eddine Kherraf Jessica Escoffier Serge Nef Pierre F Ray Christophe Arnoult |
| author_facet | Guillaume Martinez Charles Coutton Corinne Loeuillet Caroline Cazin Jana Muroňová Magalie Boguenet Emeline Lambert Magali Dhellemmes Geneviève Chevalier Jean-Pascal Hograindleur Charline Vilpreux Yasmine Neirijnck Zine-Eddine Kherraf Jessica Escoffier Serge Nef Pierre F Ray Christophe Arnoult |
| author_sort | Guillaume Martinez |
| collection | DOAJ |
| description | Male infertility is an important health concern that is expected to have a major genetic etiology. Although high-throughput sequencing has linked gene defects to more than 50% of rare and severe sperm anomalies, less than 20% of common and moderate forms are explained. We hypothesized that this low success rate could at least be partly due to oligogenic defects – the accumulation of several rare heterozygous variants in distinct, but functionally connected, genes. Here, we compared fertility and sperm parameters in male mice harboring one to four heterozygous truncating mutations of genes linked to multiple morphological anomalies of the flagellum (MMAF) syndrome. Results indicated progressively deteriorating sperm morphology and motility with increasing numbers of heterozygous mutations. This first evidence of oligogenic inheritance in failed spermatogenesis strongly suggests that oligogenic heterozygosity could explain a significant proportion of asthenoteratozoospermia cases. The findings presented pave the way to further studies in mice and man. |
| first_indexed | 2024-04-14T07:38:22Z |
| format | Article |
| id | doaj.art-50542f6b588b43b1b940b0989e0ff1de |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-14T07:38:22Z |
| publishDate | 2022-04-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-50542f6b588b43b1b940b0989e0ff1de2022-12-22T02:05:35ZengeLife Sciences Publications LtdeLife2050-084X2022-04-011110.7554/eLife.75373Oligogenic heterozygous inheritance of sperm abnormalities in mouseGuillaume Martinez0https://orcid.org/0000-0002-7572-9096Charles Coutton1Corinne Loeuillet2Caroline Cazin3Jana Muroňová4Magalie Boguenet5Emeline Lambert6Magali Dhellemmes7Geneviève Chevalier8Jean-Pascal Hograindleur9Charline Vilpreux10Yasmine Neirijnck11Zine-Eddine Kherraf12Jessica Escoffier13https://orcid.org/0000-0001-8166-5845Serge Nef14Pierre F Ray15Christophe Arnoult16https://orcid.org/0000-0002-3753-5901Institute for Advanced Biosciences, INSERM, CNRS, Université Grenoble Alpes, Grenoble, France; UM de Génétique Chromosomique, Hôpital Couple-Enfant, CHU Grenoble Alpes, Grenoble, FranceInstitute for Advanced Biosciences, INSERM, CNRS, Université Grenoble Alpes, Grenoble, France; UM de Génétique Chromosomique, Hôpital Couple-Enfant, CHU Grenoble Alpes, Grenoble, FranceInstitute for Advanced Biosciences, INSERM, CNRS, Université Grenoble Alpes, Grenoble, FranceInstitute for Advanced Biosciences, INSERM, CNRS, Université Grenoble Alpes, Grenoble, France; UM GI-DPI, CHU Grenoble Alpes, Grenoble, FranceInstitute for Advanced Biosciences, INSERM, CNRS, Université Grenoble Alpes, Grenoble, FranceInstitute for Advanced Biosciences, INSERM, CNRS, Université Grenoble Alpes, Grenoble, FranceInstitute for Advanced Biosciences, INSERM, CNRS, Université Grenoble Alpes, Grenoble, FranceInstitute for Advanced Biosciences, INSERM, CNRS, Université Grenoble Alpes, Grenoble, FranceInstitute for Advanced Biosciences, INSERM, CNRS, Université Grenoble Alpes, Grenoble, FranceInstitute for Advanced Biosciences, INSERM, CNRS, Université Grenoble Alpes, Grenoble, FranceInstitute for Advanced Biosciences, INSERM, CNRS, Université Grenoble Alpes, Grenoble, FranceDepartment of Genetic Medicine and Development, University of Geneva Medical School, Genève, SwitzerlandInstitute for Advanced Biosciences, INSERM, CNRS, Université Grenoble Alpes, Grenoble, France; UM GI-DPI, CHU Grenoble Alpes, Grenoble, FranceInstitute for Advanced Biosciences, INSERM, CNRS, Université Grenoble Alpes, Grenoble, FranceDepartment of Genetic Medicine and Development, University of Geneva Medical School, Genève, SwitzerlandInstitute for Advanced Biosciences, INSERM, CNRS, Université Grenoble Alpes, Grenoble, France; UM GI-DPI, CHU Grenoble Alpes, Grenoble, FranceInstitute for Advanced Biosciences, INSERM, CNRS, Université Grenoble Alpes, Grenoble, France; Station de Primatologie, UPS 846, CNRS, Rousset, FranceMale infertility is an important health concern that is expected to have a major genetic etiology. Although high-throughput sequencing has linked gene defects to more than 50% of rare and severe sperm anomalies, less than 20% of common and moderate forms are explained. We hypothesized that this low success rate could at least be partly due to oligogenic defects – the accumulation of several rare heterozygous variants in distinct, but functionally connected, genes. Here, we compared fertility and sperm parameters in male mice harboring one to four heterozygous truncating mutations of genes linked to multiple morphological anomalies of the flagellum (MMAF) syndrome. Results indicated progressively deteriorating sperm morphology and motility with increasing numbers of heterozygous mutations. This first evidence of oligogenic inheritance in failed spermatogenesis strongly suggests that oligogenic heterozygosity could explain a significant proportion of asthenoteratozoospermia cases. The findings presented pave the way to further studies in mice and man.https://elifesciences.org/articles/75373infertilityoligogenismhereditysperm abnormalitiesMMAF |
| spellingShingle | Guillaume Martinez Charles Coutton Corinne Loeuillet Caroline Cazin Jana Muroňová Magalie Boguenet Emeline Lambert Magali Dhellemmes Geneviève Chevalier Jean-Pascal Hograindleur Charline Vilpreux Yasmine Neirijnck Zine-Eddine Kherraf Jessica Escoffier Serge Nef Pierre F Ray Christophe Arnoult Oligogenic heterozygous inheritance of sperm abnormalities in mouse eLife infertility oligogenism heredity sperm abnormalities MMAF |
| title | Oligogenic heterozygous inheritance of sperm abnormalities in mouse |
| title_full | Oligogenic heterozygous inheritance of sperm abnormalities in mouse |
| title_fullStr | Oligogenic heterozygous inheritance of sperm abnormalities in mouse |
| title_full_unstemmed | Oligogenic heterozygous inheritance of sperm abnormalities in mouse |
| title_short | Oligogenic heterozygous inheritance of sperm abnormalities in mouse |
| title_sort | oligogenic heterozygous inheritance of sperm abnormalities in mouse |
| topic | infertility oligogenism heredity sperm abnormalities MMAF |
| url | https://elifesciences.org/articles/75373 |
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