Spata6 is required for normal assembly of the sperm connecting piece and tight head-tail conjunction.

"Pinhead sperm," or "acephalic sperm," a type of human teratozoospermia, refers to the condition in which ejaculate contains mostly sperm flagella without heads. Family clustering and homogeneity of this syndrome suggests a genetic basis, but the causative genes remain largely unknown. Here we report that Spata6, an evolutionarily conserved testis-specific gene, encodes a protein required for formation of the segmented columns and the capitulum, two major structures of the sperm connecting piece essential for linking the developing flagellum to the head during late spermiogenesis. Inactivation of Spata6 in mice leads to acephalic spermatozoa and male sterility. Our proteomic analyses reveal that SPATA6 is involved in myosin-based microfilament transport through interaction with myosin subunits (e.g., MYL6).

Lack of Spem1 causes aberrant cytoplasm removal, sperm deformation, and male infertility.

We identified a previously uncharacterized gene, spermatid maturation 1 (Spem1), encoding a protein exclusively expressed in the cytoplasm of steps 14-16 elongated spermatids in the mouse testis. This protein contains no known functional domains and is highly conserved across mammalian species. Male mice deficient in Spem1 were completely infertile because of deformed sperm characterized by a bent head wrapped around by the neck and the middle piece of the tail. We show that lack of Spem1 causes failure of the cytoplasm to become loose and detach from the head and the neck region of the developing spermatozoa. Retained cytoplasmic components mechanically obstruct the straightening of the sperm head and the stretching of the growing tail, leading to the bending of the head in the neck, followed by the wrapping of the head by the neck or the middle piece of the sperm tail. Our study reveals that proper cytoplasm removal is a genetically regulated process requiring the participation of Spem1 and that lack of Spem1 causes sperm deformation and male infertility.