DNAH10 interacts with UCHL3-PACRG complex to coordinate sperm head and flagella development during spermiogenesis

Asthenoteratozoospermia is a common underlying cause of male infertility, with dynein dysfunction playing an important role in the aetiology of the condition. Dysfunction in certain dynein proteins has been implicated in asthenoteratozoospermia, while others exclusively induce asthenozoospermia in the absence of overt morphological abnormalities in the sperm. Dynein axonemal heavy chain 10 (DNAH10), an inner dynein arm heavy chain protein, was identified as being associated with asthenoteratozoospermia in our previous studies. However, the mechanism through which DNAH10 contributes to this condition remains unclear. In this study, we demonstrated that DNAH10 deficiency leads to abnormal morphology of the sperm head and flagella. Additionally, DNAH10 dysfunction leads to impaired manchette function and aberrant localisation of axonemal proteins. Mechanistically, ubiquitin carboxyl-terminal hydrolase L3 (UCHL3) binds to parkin co-regulated gene protein (PACRG) and stabilises it via deubiquitination. In this process, DNAH10 exerts a bridging effect, enhancing the interaction between the UCHL3-PACRG complex to facilitate their involvement in manchette function. Collectively, this study demonstrated the function of DNAH10 in intra-manchette transport, providing important guidance for genetic diagnosis and prognosis in patients with infertility.