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CFAP70 is a solid and valuable target for the genetic diagnosis of oligo-astheno-teratozoospermia in infertile men

BACKGROUND: Male infertility is a worldwide population health concern, but its aetiology remains largely understood. Although CFAP70 variants have already been reported in two oligo-astheno-teratozoospermia (OAT) individuals by sequencing, animal evidence to support CFAP70 as a credible OAT-pathogen...

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Autores principales: Jin, Hui-Juan, Wang, Jun-Li, Geng, Xin-Yan, Wang, Chun-Yan, Wang, Bin-Bin, Chen, Su-Ren
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10333438/
https://www.ncbi.nlm.nih.gov/pubmed/37352829
http://dx.doi.org/10.1016/j.ebiom.2023.104675
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author Jin, Hui-Juan
Wang, Jun-Li
Geng, Xin-Yan
Wang, Chun-Yan
Wang, Bin-Bin
Chen, Su-Ren
author_facet Jin, Hui-Juan
Wang, Jun-Li
Geng, Xin-Yan
Wang, Chun-Yan
Wang, Bin-Bin
Chen, Su-Ren
author_sort Jin, Hui-Juan
collection PubMed
description BACKGROUND: Male infertility is a worldwide population health concern, but its aetiology remains largely understood. Although CFAP70 variants have already been reported in two oligo-astheno-teratozoospermia (OAT) individuals by sequencing, animal evidence to support CFAP70 as a credible OAT-pathogenic gene is lacking. METHOD: Cfap70-KO mice were generated to explore the physiological role of CFAP70. CFAP70 variants were detected in infertile men with OAT by whole exome sequencing and Sanger sequencing confirmation. Cfap70-truncated mice were further generated to explore the pathogenicity of the nonsense variant of CFAP70 identified in the proband. FINDINGS: Here, we demonstrate that Cfap70-KO mice are sterile mainly due to OAT and further identify a Chinese infertile man carrying a homozygous nonsense variant (c.2962C > T/p.R988X) of CFAP70. Cfap70-truncated mice lacking 5–8 tetratricopeptide repeats (TPRs) mimic the patient's symptoms. CFAP70 is required for the biogenesis of spermatid flagella partially by regulating the expression of OAT-associated proteins (e.g., QRICH2), assisting the cytoplasmic preassembly of the calmodulin- and radial spoke-associated complex (CSC), and controlling the manchette localization of axoneme-related proteins. Moreover, we suggest that CFAP70-associated male infertility could be overcome by intracytoplasmic sperm injection (ICSI) treatment. INTERPRETATION: Overall, we demonstrate that CFAP70 is necessary to assemble spermatid flagella and that CFAP70 gene could be used as a diagnostic target for male infertility with OAT in the clinic. FUNDING: This study was supported by the 10.13039/501100012166National Key Research and Development Project (2019YFA0802101 to S.C), Open Fund of Key Laboratory of Cell Proliferation and Regulation Biology, 10.13039/501100002338Ministry of Education (to S.C), Central Government to Guide Local Scientific and Technological Development (ZY21195023 to B.W), and Basic Research Projects of Central Scientific Research Institutes (to B.W).
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spelling pubmed-103334382023-07-12 CFAP70 is a solid and valuable target for the genetic diagnosis of oligo-astheno-teratozoospermia in infertile men Jin, Hui-Juan Wang, Jun-Li Geng, Xin-Yan Wang, Chun-Yan Wang, Bin-Bin Chen, Su-Ren eBioMedicine Articles BACKGROUND: Male infertility is a worldwide population health concern, but its aetiology remains largely understood. Although CFAP70 variants have already been reported in two oligo-astheno-teratozoospermia (OAT) individuals by sequencing, animal evidence to support CFAP70 as a credible OAT-pathogenic gene is lacking. METHOD: Cfap70-KO mice were generated to explore the physiological role of CFAP70. CFAP70 variants were detected in infertile men with OAT by whole exome sequencing and Sanger sequencing confirmation. Cfap70-truncated mice were further generated to explore the pathogenicity of the nonsense variant of CFAP70 identified in the proband. FINDINGS: Here, we demonstrate that Cfap70-KO mice are sterile mainly due to OAT and further identify a Chinese infertile man carrying a homozygous nonsense variant (c.2962C > T/p.R988X) of CFAP70. Cfap70-truncated mice lacking 5–8 tetratricopeptide repeats (TPRs) mimic the patient's symptoms. CFAP70 is required for the biogenesis of spermatid flagella partially by regulating the expression of OAT-associated proteins (e.g., QRICH2), assisting the cytoplasmic preassembly of the calmodulin- and radial spoke-associated complex (CSC), and controlling the manchette localization of axoneme-related proteins. Moreover, we suggest that CFAP70-associated male infertility could be overcome by intracytoplasmic sperm injection (ICSI) treatment. INTERPRETATION: Overall, we demonstrate that CFAP70 is necessary to assemble spermatid flagella and that CFAP70 gene could be used as a diagnostic target for male infertility with OAT in the clinic. FUNDING: This study was supported by the 10.13039/501100012166National Key Research and Development Project (2019YFA0802101 to S.C), Open Fund of Key Laboratory of Cell Proliferation and Regulation Biology, 10.13039/501100002338Ministry of Education (to S.C), Central Government to Guide Local Scientific and Technological Development (ZY21195023 to B.W), and Basic Research Projects of Central Scientific Research Institutes (to B.W). Elsevier 2023-06-21 /pmc/articles/PMC10333438/ /pubmed/37352829 http://dx.doi.org/10.1016/j.ebiom.2023.104675 Text en © 2023 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Articles
Jin, Hui-Juan
Wang, Jun-Li
Geng, Xin-Yan
Wang, Chun-Yan
Wang, Bin-Bin
Chen, Su-Ren
CFAP70 is a solid and valuable target for the genetic diagnosis of oligo-astheno-teratozoospermia in infertile men
title CFAP70 is a solid and valuable target for the genetic diagnosis of oligo-astheno-teratozoospermia in infertile men
title_full CFAP70 is a solid and valuable target for the genetic diagnosis of oligo-astheno-teratozoospermia in infertile men
title_fullStr CFAP70 is a solid and valuable target for the genetic diagnosis of oligo-astheno-teratozoospermia in infertile men
title_full_unstemmed CFAP70 is a solid and valuable target for the genetic diagnosis of oligo-astheno-teratozoospermia in infertile men
title_short CFAP70 is a solid and valuable target for the genetic diagnosis of oligo-astheno-teratozoospermia in infertile men
title_sort cfap70 is a solid and valuable target for the genetic diagnosis of oligo-astheno-teratozoospermia in infertile men
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10333438/
https://www.ncbi.nlm.nih.gov/pubmed/37352829
http://dx.doi.org/10.1016/j.ebiom.2023.104675
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