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Open Access 01-12-2021 | ICSI | Research

Novel variants in DNAH9 lead to nonsyndromic severe asthenozoospermia

Authors: Dongdong Tang, Yanwei Sha, Yang Gao, Jingjing Zhang, Huiru Cheng, Junqiang Zhang, Xiaoqing Ni, Chao Wang, Chuan Xu, Hao Geng, Xiaojin He, Yunxia Cao

Published in: Reproductive Biology and Endocrinology | Issue 1/2021

Abstract

Background

Asthenozoospermia is one of the most common causes of male infertility, and its genetic etiology is poorly understood. DNAH9 is a core component of outer dynein arms in cilia and flagellum. It was reported that variants of DNAH9 (OMIM: 603330) might cause primary ciliary dyskinesia (PCD). However, variants in DNAH9 lead to nonsyndromic severe asthenozoospermia have yet to be reported.

Methods

Whole exome sequencing (WES) was performed for two individuals with nonsyndromic severe asthenozoospermia from two non-consanguineous families, and Sanger sequencing was performed to verify the identified variants and parental origins. Sperm routine analysis, sperm vitality rate and sperm morphology analysis were performed according the WHO guidelines 2010 (5th edition). Transmission electron microscopy (TEM, TECNAI-10, 80 kV, Philips, Holland) was used to observe ultrastructures of sperm tail. Quantitative realtime-PCR and immunofluorescence staining were performed to detect the expression of DNAH9-mRNA and location of DNAH9-protein. Furthermore, assisted reproductive procedures were applied.

Results

By WES and Sanger sequencing, compound heterozygous DNAH9 (NM_001372.4) variants were identified in the two individuals with nonsyndromic severe asthenozoospermia (F1 II-1: c.302dupT, p.Leu101fs*47 / c.6956A > G, p.Asp2319Gly; F2 II-1: c.6294 T > A, p.Phe2098Leu / c.10571 T > A, p.Leu3524Gln). Progressive rates less than 1% with normal sperm morphology rates and normal vitality rates were found in both of the two subjects. No respiratory phenotypes, situs inversus or other malformations were found by detailed medical history, physical examination and lung CT scans etc. Moreover, the expression of DNAH9-mRNA was significantly decreased in sperm from F1 II-1. And expression of DNAH9 is lower in sperm tail by immunofluorescence staining in F1 II-1 compared with normal control. Notably, by intracytoplasmic sperm injection (ICSI), F1 II-1 and his partner successfully achieved clinical pregnancy.

Conclusions

We identified DNAH9 as a novel pathogenic gene for nonsyndromic severe asthenospermia, and ICSI can contribute to favorable pregnancy outcomes for these patients.

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Title: Novel variants in DNAH9 lead to nonsyndromic severe asthenozoospermia
Authors: Dongdong Tang
Yanwei Sha
Yang Gao
Jingjing Zhang
Huiru Cheng
Junqiang Zhang
Xiaoqing Ni
Chao Wang
Chuan Xu
Hao Geng
Xiaojin He
Yunxia Cao
Publication date: 01-12-2021
Publisher: BioMed Central
Keyword: ICSI
Published in: Reproductive Biology and Endocrinology / Issue 1/2021
Electronic ISSN: 1477-7827
DOI: https://doi.org/10.1186/s12958-021-00709-0

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Novel variants in DNAH9 lead to nonsyndromic severe asthenozoospermia

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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