AXDND1, a novel testis-enriched gene, is required for spermiogenesis and male fertility

Abstract 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 fo...

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Autores principales:	Qian Ma, Congcong Cao, Changshui Zhuang, Xiaomin Luo, Xiaofeng Li, Huijuan Wan, Jing Ye, Fangfang Chen, Lina Cui, Yan Zhang, Yujiao Wen, Shuiqiao Yuan, Yaoting Gui
Formato:	article
Lenguaje:	EN
Publicado:	Nature Publishing Group 2021
Materias:	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Cytology QH573-671
Acceso en línea:	https://doaj.org/article/a10f44fc328f46dbb10e63da1b57cfc2
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spelling	oai:doaj.org-article:a10f44fc328f46dbb10e63da1b57cfc22021-11-14T12:12:34ZAXDND1, a novel testis-enriched gene, is required for spermiogenesis and male fertility10.1038/s41420-021-00738-z2058-7716https://doaj.org/article/a10f44fc328f46dbb10e63da1b57cfc22021-11-01T00:00:00Zhttps://doi.org/10.1038/s41420-021-00738-zhttps://doaj.org/toc/2058-7716Abstract 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.Qian MaCongcong CaoChangshui ZhuangXiaomin LuoXiaofeng LiHuijuan WanJing YeFangfang ChenLina CuiYan ZhangYujiao WenShuiqiao YuanYaoting GuiNature Publishing GrouparticleNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282CytologyQH573-671ENCell Death Discovery, Vol 7, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Cytology QH573-671
spellingShingle	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Cytology QH573-671 Qian Ma Congcong Cao Changshui Zhuang Xiaomin Luo Xiaofeng Li Huijuan Wan Jing Ye Fangfang Chen Lina Cui Yan Zhang Yujiao Wen Shuiqiao Yuan Yaoting Gui AXDND1, a novel testis-enriched gene, is required for spermiogenesis and male fertility
description	Abstract 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	article
author	Qian Ma Congcong Cao Changshui Zhuang Xiaomin Luo Xiaofeng Li Huijuan Wan Jing Ye Fangfang Chen Lina Cui Yan Zhang Yujiao Wen Shuiqiao Yuan Yaoting Gui
author_facet	Qian Ma Congcong Cao Changshui Zhuang Xiaomin Luo Xiaofeng Li Huijuan Wan Jing Ye Fangfang Chen Lina Cui Yan Zhang Yujiao Wen Shuiqiao Yuan Yaoting Gui
author_sort	Qian Ma
title	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_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_sort	axdnd1, a novel testis-enriched gene, is required for spermiogenesis and male fertility
publisher	Nature Publishing Group
publishDate	2021
url	https://doaj.org/article/a10f44fc328f46dbb10e63da1b57cfc2
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AXDND1, a novel testis-enriched gene, is required for spermiogenesis and male fertility

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