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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...

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Autores principales: Martinez, Guillaume, Coutton, Charles, Loeuillet, Corinne, Cazin, Caroline, Muroňová, Jana, Boguenet, Magalie, Lambert, Emeline, Dhellemmes, Magali, Chevalier, Geneviève, Hograindleur, Jean-Pascal, Vilpreux, Charline, Neirijnck, Yasmine, Kherraf, Zine-Eddine, Escoffier, Jessica, Nef, Serge, Ray, Pierre F, Arnoult, Christophe
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9071268/
https://www.ncbi.nlm.nih.gov/pubmed/35451961
http://dx.doi.org/10.7554/eLife.75373
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author Martinez, Guillaume
Coutton, Charles
Loeuillet, Corinne
Cazin, Caroline
Muroňová, Jana
Boguenet, Magalie
Lambert, Emeline
Dhellemmes, Magali
Chevalier, Geneviève
Hograindleur, Jean-Pascal
Vilpreux, Charline
Neirijnck, Yasmine
Kherraf, Zine-Eddine
Escoffier, Jessica
Nef, Serge
Ray, Pierre F
Arnoult, Christophe
author_facet Martinez, Guillaume
Coutton, Charles
Loeuillet, Corinne
Cazin, Caroline
Muroňová, Jana
Boguenet, Magalie
Lambert, Emeline
Dhellemmes, Magali
Chevalier, Geneviève
Hograindleur, Jean-Pascal
Vilpreux, Charline
Neirijnck, Yasmine
Kherraf, Zine-Eddine
Escoffier, Jessica
Nef, Serge
Ray, Pierre F
Arnoult, Christophe
author_sort Martinez, Guillaume
collection PubMed
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.
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spelling pubmed-90712682022-05-06 Oligogenic heterozygous inheritance of sperm abnormalities in mouse Martinez, Guillaume Coutton, Charles Loeuillet, Corinne Cazin, Caroline Muroňová, Jana Boguenet, Magalie Lambert, Emeline Dhellemmes, Magali Chevalier, Geneviève Hograindleur, Jean-Pascal Vilpreux, Charline Neirijnck, Yasmine Kherraf, Zine-Eddine Escoffier, Jessica Nef, Serge Ray, Pierre F Arnoult, Christophe eLife Cell Biology 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. eLife Sciences Publications, Ltd 2022-04-22 /pmc/articles/PMC9071268/ /pubmed/35451961 http://dx.doi.org/10.7554/eLife.75373 Text en © 2022, Martinez et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Cell Biology
Martinez, Guillaume
Coutton, Charles
Loeuillet, Corinne
Cazin, Caroline
Muroňová, Jana
Boguenet, Magalie
Lambert, Emeline
Dhellemmes, Magali
Chevalier, Geneviève
Hograindleur, Jean-Pascal
Vilpreux, Charline
Neirijnck, Yasmine
Kherraf, Zine-Eddine
Escoffier, Jessica
Nef, Serge
Ray, Pierre F
Arnoult, Christophe
Oligogenic heterozygous inheritance of sperm abnormalities in mouse
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 Cell Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9071268/
https://www.ncbi.nlm.nih.gov/pubmed/35451961
http://dx.doi.org/10.7554/eLife.75373
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