Cargando…
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...
Autores principales: | , , , , , , , , , , , , , , , , |
---|---|
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 |
_version_ | 1784700816666394624 |
---|---|
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. |
format | Online Article Text |
id | pubmed-9071268 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT martinezguillaume oligogenicheterozygousinheritanceofspermabnormalitiesinmouse AT couttoncharles oligogenicheterozygousinheritanceofspermabnormalitiesinmouse AT loeuilletcorinne oligogenicheterozygousinheritanceofspermabnormalitiesinmouse AT cazincaroline oligogenicheterozygousinheritanceofspermabnormalitiesinmouse AT muronovajana oligogenicheterozygousinheritanceofspermabnormalitiesinmouse AT boguenetmagalie oligogenicheterozygousinheritanceofspermabnormalitiesinmouse AT lambertemeline oligogenicheterozygousinheritanceofspermabnormalitiesinmouse AT dhellemmesmagali oligogenicheterozygousinheritanceofspermabnormalitiesinmouse AT chevaliergenevieve oligogenicheterozygousinheritanceofspermabnormalitiesinmouse AT hograindleurjeanpascal oligogenicheterozygousinheritanceofspermabnormalitiesinmouse AT vilpreuxcharline oligogenicheterozygousinheritanceofspermabnormalitiesinmouse AT neirijnckyasmine oligogenicheterozygousinheritanceofspermabnormalitiesinmouse AT kherrafzineeddine oligogenicheterozygousinheritanceofspermabnormalitiesinmouse AT escoffierjessica oligogenicheterozygousinheritanceofspermabnormalitiesinmouse AT nefserge oligogenicheterozygousinheritanceofspermabnormalitiesinmouse AT raypierref oligogenicheterozygousinheritanceofspermabnormalitiesinmouse AT arnoultchristophe oligogenicheterozygousinheritanceofspermabnormalitiesinmouse |