CFAP70 is a solid and valuable target for the genetic diagnosis of oligo-astheno-teratozoospermia in infertile menResearch in context
Summary: 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 OA...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-07-01
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| Series: | EBioMedicine |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396423002402 |
| _version_ | 1797797987091480576 |
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| author | Hui-Juan Jin Jun-Li Wang Xin-Yan Geng Chun-Yan Wang Bin-Bin Wang Su-Ren Chen |
| author_facet | Hui-Juan Jin Jun-Li Wang Xin-Yan Geng Chun-Yan Wang Bin-Bin Wang Su-Ren Chen |
| author_sort | Hui-Juan Jin |
| collection | DOAJ |
| description | Summary: 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 National Key Research and Development Project (2019YFA0802101 to S.C), Open Fund of Key Laboratory of Cell Proliferation and Regulation Biology, Ministry 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). |
| first_indexed | 2024-03-13T03:56:38Z |
| format | Article |
| id | doaj.art-21afe3d4489243e3ac9ad370de83cdc9 |
| institution | Directory Open Access Journal |
| issn | 2352-3964 |
| language | English |
| last_indexed | 2024-03-13T03:56:38Z |
| publishDate | 2023-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EBioMedicine |
| spelling | doaj.art-21afe3d4489243e3ac9ad370de83cdc92023-06-22T05:04:19ZengElsevierEBioMedicine2352-39642023-07-0193104675CFAP70 is a solid and valuable target for the genetic diagnosis of oligo-astheno-teratozoospermia in infertile menResearch in contextHui-Juan Jin0Jun-Li Wang1Xin-Yan Geng2Chun-Yan Wang3Bin-Bin Wang4Su-Ren Chen5Key Laboratory of Cell Proliferation and Regulation Biology, Ministry of Education, Department of Biology, College of Life Sciences, Beijing Normal University, Beijing, 100875, ChinaCenter of Reproductive Medicine, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, 533000, Guangxi, China; Environmental Health Risk Assessment and Prevention Engineering Center of Ecological Aluminum Industry Base of Youjiang Medical University for Nationalities, Baise, 533000, Guangxi, ChinaKey Laboratory of Cell Proliferation and Regulation Biology, Ministry of Education, Department of Biology, College of Life Sciences, Beijing Normal University, Beijing, 100875, ChinaCenter for Genetics, National Research Institute of Family Planning, Beijing, 100081, China; Graduate School of Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing, 100005, ChinaCenter for Genetics, National Research Institute of Family Planning, Beijing, 100081, China; Graduate School of Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing, 100005, China; NHC Key Laboratory of Reproductive Health Engineering Technology Research (NRIFP), National Research Institute for Family Planning, 100081 Beijing, China; Corresponding author. Center for Genetics, National Research Institute of Family Planning, Beijing, 100081, China.Key Laboratory of Cell Proliferation and Regulation Biology, Ministry of Education, Department of Biology, College of Life Sciences, Beijing Normal University, Beijing, 100875, China; Corresponding author. Key Laboratory of Cell Proliferation and Regulation Biology, Ministry of Education, Department of Biology, College of Life Sciences, Beijing Normal University, Beijing, 100875, China.Summary: 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 National Key Research and Development Project (2019YFA0802101 to S.C), Open Fund of Key Laboratory of Cell Proliferation and Regulation Biology, Ministry 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).http://www.sciencedirect.com/science/article/pii/S2352396423002402Male infertilityOligo-astheno-teratozoospermiaCFAP70Knockout miceSperm flagellar assembly |
| spellingShingle | Hui-Juan Jin Jun-Li Wang Xin-Yan Geng Chun-Yan Wang Bin-Bin Wang Su-Ren Chen CFAP70 is a solid and valuable target for the genetic diagnosis of oligo-astheno-teratozoospermia in infertile menResearch in context EBioMedicine Male infertility Oligo-astheno-teratozoospermia CFAP70 Knockout mice Sperm flagellar assembly |
| title | CFAP70 is a solid and valuable target for the genetic diagnosis of oligo-astheno-teratozoospermia in infertile menResearch in context |
| title_full | CFAP70 is a solid and valuable target for the genetic diagnosis of oligo-astheno-teratozoospermia in infertile menResearch in context |
| title_fullStr | CFAP70 is a solid and valuable target for the genetic diagnosis of oligo-astheno-teratozoospermia in infertile menResearch in context |
| title_full_unstemmed | CFAP70 is a solid and valuable target for the genetic diagnosis of oligo-astheno-teratozoospermia in infertile menResearch in context |
| title_short | CFAP70 is a solid and valuable target for the genetic diagnosis of oligo-astheno-teratozoospermia in infertile menResearch in context |
| title_sort | cfap70 is a solid and valuable target for the genetic diagnosis of oligo astheno teratozoospermia in infertile menresearch in context |
| topic | Male infertility Oligo-astheno-teratozoospermia CFAP70 Knockout mice Sperm flagellar assembly |
| url | http://www.sciencedirect.com/science/article/pii/S2352396423002402 |
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