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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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Detalles Bibliográficos
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
Descripción
Sumario: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.