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A novel mutation in CFAP47 causes male infertility due to multiple morphological abnormalities of the sperm flagella

INTRODUCTION: A previous study suggested that loss of CFAP47 function is involved in multiple morphological abnormalities of the sperm flagella (MMAF) in humans and mice. However, the comprehensive role of CFAP47 in spermatogenesis is largely unknown. METHODS: Whole-exome sequencing (WES) was conduc...

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Autores principales: Liu, Mohan, Dai, Siyu, Zhang, Jiying, Yang, Yihong, Shen, Ying, Liu, Hongqian, Yang, Yanting, Jiang, Chuan, Tian, Erpo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10326514/
https://www.ncbi.nlm.nih.gov/pubmed/37424856
http://dx.doi.org/10.3389/fendo.2023.1155639
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author Liu, Mohan
Dai, Siyu
Zhang, Jiying
Yang, Yihong
Shen, Ying
Liu, Hongqian
Yang, Yanting
Jiang, Chuan
Tian, Erpo
author_facet Liu, Mohan
Dai, Siyu
Zhang, Jiying
Yang, Yihong
Shen, Ying
Liu, Hongqian
Yang, Yanting
Jiang, Chuan
Tian, Erpo
author_sort Liu, Mohan
collection PubMed
description INTRODUCTION: A previous study suggested that loss of CFAP47 function is involved in multiple morphological abnormalities of the sperm flagella (MMAF) in humans and mice. However, the comprehensive role of CFAP47 in spermatogenesis is largely unknown. METHODS: Whole-exome sequencing (WES) was conducted to identify pathogenic variant in two patients with MMAF. The functional effect of the identified mutations was investigated by immunofluorescence staining and western blotting. Intracytoplasmic sperm injection (ICSI) was used to assist fertilization for the patient with MMAF. RESULTS: In this study, we identified a novel missense mutation (c.1414G>A; p.V472M) in CFAP47 in two unrelated patients with oligoasthenoteratozoospermia. Intriguingly, in addition to the MMAF phenotype very analogous to the previous report, the two patients notably presented abnormal morphology of sperm heads, the sperm mitochondrial sheath was obviously disorganized, and the sperm annulus were almost defective. Further functional experiments confirmed that the expression of CFAP47 was markedly reduced in the spermatozoa of the patients. Mechanism analysis suggested that CFAP47 might regulate the expression of CFAP65, CFAP69 and SEPTIN4 through their physical interactions and thus modulating sperm morphogenesis. CONCLUSION: we revealed a novel mutation in CFAP47 and further expanded the phenotype and mutation spectrum of CFAP47, as well as the potential mechanism of CFAP47 manipulating spermatogenesis, finally providing important guidance for genetic counseling and targeted treatment for CFAP47 mutation-related male infertility.
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spelling pubmed-103265142023-07-08 A novel mutation in CFAP47 causes male infertility due to multiple morphological abnormalities of the sperm flagella Liu, Mohan Dai, Siyu Zhang, Jiying Yang, Yihong Shen, Ying Liu, Hongqian Yang, Yanting Jiang, Chuan Tian, Erpo Front Endocrinol (Lausanne) Endocrinology INTRODUCTION: A previous study suggested that loss of CFAP47 function is involved in multiple morphological abnormalities of the sperm flagella (MMAF) in humans and mice. However, the comprehensive role of CFAP47 in spermatogenesis is largely unknown. METHODS: Whole-exome sequencing (WES) was conducted to identify pathogenic variant in two patients with MMAF. The functional effect of the identified mutations was investigated by immunofluorescence staining and western blotting. Intracytoplasmic sperm injection (ICSI) was used to assist fertilization for the patient with MMAF. RESULTS: In this study, we identified a novel missense mutation (c.1414G>A; p.V472M) in CFAP47 in two unrelated patients with oligoasthenoteratozoospermia. Intriguingly, in addition to the MMAF phenotype very analogous to the previous report, the two patients notably presented abnormal morphology of sperm heads, the sperm mitochondrial sheath was obviously disorganized, and the sperm annulus were almost defective. Further functional experiments confirmed that the expression of CFAP47 was markedly reduced in the spermatozoa of the patients. Mechanism analysis suggested that CFAP47 might regulate the expression of CFAP65, CFAP69 and SEPTIN4 through their physical interactions and thus modulating sperm morphogenesis. CONCLUSION: we revealed a novel mutation in CFAP47 and further expanded the phenotype and mutation spectrum of CFAP47, as well as the potential mechanism of CFAP47 manipulating spermatogenesis, finally providing important guidance for genetic counseling and targeted treatment for CFAP47 mutation-related male infertility. Frontiers Media S.A. 2023-06-23 /pmc/articles/PMC10326514/ /pubmed/37424856 http://dx.doi.org/10.3389/fendo.2023.1155639 Text en Copyright © 2023 Liu, Dai, Zhang, Yang, Shen, Liu, Yang, Jiang and Tian https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Endocrinology
Liu, Mohan
Dai, Siyu
Zhang, Jiying
Yang, Yihong
Shen, Ying
Liu, Hongqian
Yang, Yanting
Jiang, Chuan
Tian, Erpo
A novel mutation in CFAP47 causes male infertility due to multiple morphological abnormalities of the sperm flagella
title A novel mutation in CFAP47 causes male infertility due to multiple morphological abnormalities of the sperm flagella
title_full A novel mutation in CFAP47 causes male infertility due to multiple morphological abnormalities of the sperm flagella
title_fullStr A novel mutation in CFAP47 causes male infertility due to multiple morphological abnormalities of the sperm flagella
title_full_unstemmed A novel mutation in CFAP47 causes male infertility due to multiple morphological abnormalities of the sperm flagella
title_short A novel mutation in CFAP47 causes male infertility due to multiple morphological abnormalities of the sperm flagella
title_sort novel mutation in cfap47 causes male infertility due to multiple morphological abnormalities of the sperm flagella
topic Endocrinology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10326514/
https://www.ncbi.nlm.nih.gov/pubmed/37424856
http://dx.doi.org/10.3389/fendo.2023.1155639
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