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AXDND1, a novel testis-enriched gene, is required for spermiogenesis and male fertility
Spermiogenesis is a complex process depending on the sophisticated coordination of a myriad of testis-enriched gene regulations. The regulatory pathways that coordinate this process are not well understood, and we demonstrate here that AXDND1, as a novel testis-enriched gene is essential for spermio...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8580973/ https://www.ncbi.nlm.nih.gov/pubmed/34759295 http://dx.doi.org/10.1038/s41420-021-00738-z |
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author | Ma, Qian Cao, Congcong Zhuang, Changshui Luo, Xiaomin Li, Xiaofeng Wan, Huijuan Ye, Jing Chen, Fangfang Cui, Lina Zhang, Yan Wen, Yujiao Yuan, Shuiqiao Gui, Yaoting |
author_facet | Ma, Qian Cao, Congcong Zhuang, Changshui Luo, Xiaomin Li, Xiaofeng Wan, Huijuan Ye, Jing Chen, Fangfang Cui, Lina Zhang, Yan Wen, Yujiao Yuan, Shuiqiao Gui, Yaoting |
author_sort | Ma, Qian |
collection | PubMed |
description | Spermiogenesis is a complex process depending on the sophisticated coordination of a myriad of testis-enriched gene regulations. The regulatory pathways that coordinate this process are not well understood, and we demonstrate here that AXDND1, as a novel testis-enriched gene is essential for spermiogenesis and male fertility. AXDND1 is exclusively expressed in the round and elongating spermatids in humans and mice. We identified two potentially deleterious mutations of AXDND1 unique to non‐obstructive azoospermia (NOA) patients through selected exonic sequencing. Importantly, Axdnd1 knockout males are sterile with reduced testis size caused by increased germ cell apoptosis and sloughing, exhibiting phenotypes consistent with oligoasthenoteratozoospermia. Axdnd1 mutated late spermatids showed head deformation, outer doublet microtubules deficiency in the axoneme, and loss of corresponding accessory structures, including outer dense fiber (ODF) and mitochondria sheath. These phenotypes were probably due to the perturbed behavior of the manchette, a dynamic structure where AXDND1 was localized. Our findings establish AXDND1 as a novel testis-enrich gene essential for spermiogenesis and male fertility probably by regulating the manchette dynamics, spermatid head shaping, sperm flagellum assembly. |
format | Online Article Text |
id | pubmed-8580973 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-85809732021-11-15 AXDND1, a novel testis-enriched gene, is required for spermiogenesis and male fertility Ma, Qian Cao, Congcong Zhuang, Changshui Luo, Xiaomin Li, Xiaofeng Wan, Huijuan Ye, Jing Chen, Fangfang Cui, Lina Zhang, Yan Wen, Yujiao Yuan, Shuiqiao Gui, Yaoting Cell Death Discov Article Spermiogenesis is a complex process depending on the sophisticated coordination of a myriad of testis-enriched gene regulations. The regulatory pathways that coordinate this process are not well understood, and we demonstrate here that AXDND1, as a novel testis-enriched gene is essential for spermiogenesis and male fertility. AXDND1 is exclusively expressed in the round and elongating spermatids in humans and mice. We identified two potentially deleterious mutations of AXDND1 unique to non‐obstructive azoospermia (NOA) patients through selected exonic sequencing. Importantly, Axdnd1 knockout males are sterile with reduced testis size caused by increased germ cell apoptosis and sloughing, exhibiting phenotypes consistent with oligoasthenoteratozoospermia. Axdnd1 mutated late spermatids showed head deformation, outer doublet microtubules deficiency in the axoneme, and loss of corresponding accessory structures, including outer dense fiber (ODF) and mitochondria sheath. These phenotypes were probably due to the perturbed behavior of the manchette, a dynamic structure where AXDND1 was localized. Our findings establish AXDND1 as a novel testis-enrich gene essential for spermiogenesis and male fertility probably by regulating the manchette dynamics, spermatid head shaping, sperm flagellum assembly. Nature Publishing Group UK 2021-11-11 /pmc/articles/PMC8580973/ /pubmed/34759295 http://dx.doi.org/10.1038/s41420-021-00738-z Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Ma, Qian Cao, Congcong Zhuang, Changshui Luo, Xiaomin Li, Xiaofeng Wan, Huijuan Ye, Jing Chen, Fangfang Cui, Lina Zhang, Yan Wen, Yujiao Yuan, Shuiqiao Gui, Yaoting AXDND1, a novel testis-enriched gene, is required for spermiogenesis and male fertility |
title | AXDND1, a novel testis-enriched gene, is required for spermiogenesis and male fertility |
title_full | AXDND1, a novel testis-enriched gene, is required for spermiogenesis and male fertility |
title_fullStr | AXDND1, a novel testis-enriched gene, is required for spermiogenesis and male fertility |
title_full_unstemmed | AXDND1, a novel testis-enriched gene, is required for spermiogenesis and male fertility |
title_short | AXDND1, a novel testis-enriched gene, is required for spermiogenesis and male fertility |
title_sort | axdnd1, a novel testis-enriched gene, is required for spermiogenesis and male fertility |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8580973/ https://www.ncbi.nlm.nih.gov/pubmed/34759295 http://dx.doi.org/10.1038/s41420-021-00738-z |
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