Loss of function mutation in DNAH7 induces male infertility associated with abnormalities of the sperm flagella and mitochondria in human.

Male infertility is an increasingly serious health problem affecting couples of reproductive age. Mutations in axoneme-associated genes cause male infertility. Dynein arm proteins are essential in sustaining normal axonemes and promote flagellar motility. However, the function of DNAH7 in male fertility in vivo remains unclear. Herein, we showed that DNAH7 disruption in humans results in male infertility, which was characterised by multiple morphological abnormalities of sperm flagella. The axoneme structure of the sperm from a DNAH7-deficient patient revealed the loss of inner dynein arms. Moreover, the mitochondria of the sperm flagella detached and dispersed outside the axoneme, leading to abnormalities in the mitochondrial sheath in the mid-piece region. Live birth was achieved via intracytoplasmic sperm injection. Thus, DNAH7 is critical for axoneme and mitochondrial development in human sperm. These findings further clarify the spectrum of DNAH7 biology and provide new insights for diagnosing infertility and treating patients harbouring DNAH7 mutations.