Delta tubulin stabilizes male meiotic kinetochores and aids microtubule remodeling and fertility.

Delta tubulin (TUBD1) is a noncanonical tubulin protein that has been linked to complex microtubule structures in somatic cell lines and unicellular species. Its role in mammals remains enigmatic; however, TUBD1 is enriched within mammalian male germ cells. Herein, we have defined new roles for TUBD1 during male germ cell development in vivo using a conditional knockout mouse model and shown that spermatogenesis in the absence of TUBD1 causes sterility.

A novel CCDC112-dependent process of sperm midpiece formation and epididymal maturation.

The sperm mitochondrial sheath has proposed functions in structural support and energy production for motility. Here we define coiled coil domain containing protein 112, CCDC112, as crucial for male fertility, specifically in the assembly and function of the mitochondrial sheath. We unveiled a previously unrecognised process of epididymal mitochondrial sheath maturation.

AXDND1 is required to balance spermatogonial commitment and for sperm tail formation in mice and humans.

Dynein complexes are large, multi-unit assemblies involved in many biological processes via their critical roles in protein transport and axoneme motility. Using next-generation sequencing of infertile men presenting with low or no sperm in their ejaculates, we identified damaging variants in the dynein-related gene AXDND1. We thus hypothesised that AXDND1 is a critical regulator of male fertility.

Genetic mutation of results in male infertility due to abnormal sperm tail composition.

The transition zone is a specialised gate at the base of cilia/flagella, which separates the ciliary compartment from the cytoplasm and strictly regulates protein entry. We identified a potential new regulator of the male germ cell transition zone, CEP76. We demonstrated that CEP76 was involved in the selective entry and incorporation of key proteins required for sperm function and fertility into the ciliary compartment and ultimately the sperm tail.