ArticleAsian journal of andrology2026
Novel homozygous or compound heterozygous DNAH17 variants lead to male infertility characterized by multiple morphological abnormalities of the sperm flagella and asthenoteratozoospermia in humans.
Article in Asian journal of andrology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Genetic variants in the dynein axonemal heavy chain 17 ( DNAH17 ) have been implicated in multiple morphological abnormalities of the sperm flagella (MMAF) and asthenoteratozoospermia (ATZS). The aim of this study is to identify novel DNAH17 variants associated with MMAF and ATZS and to evaluate the impact of these variants on sperm motility, sperm morphology, the ultrastructure of sperm flagella, and the outcomes of intracytoplasmic sperm injection (ICSI). In the present study, we identified one novel homozygous and three compound heterozygous DNAH17 variants in one consanguineous and three nonconsanguineous families. Semen analysis revealed significant reductions in sperm motility and notable morphological changes. Transmission electron microscopy (TEM) revealed the absence of outer dynein arms (ODAs), loss of peripheral doublet microtubules (DMTs) 4-7, and multiple mitochondrial sheath (MS) abnormalities in the sperm flagella. Functional analyses indicated that these variants disrupted the expression and localization of the DNAH17 protein in the sperm flagella. Tandem mass tagging proteomics and immunofluorescence demonstrated a significant reduction in the expression of proteins associated with the assembly of ODA-associated proteins into the axoneme from individuals with DNAH17 variants. Notably, successful pregnancies were achieved through ICSI combined with assisted oocyte activation (AOA) treatment in the female partner of these probands. This study identified seven novel homozygous or compound heterozygous DNAH17 variants in both consanguineous and nonconsanguineous families, highlighting their detrimental effects on sperm motility, morphology, and flagellar ultrastructure. These findings provide valuable insights for the genetic diagnosis of MMAF and may enhance future genetic counseling strategies.
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