The Expression And Functions Of SPATA46 During Mouse Spermatogenesis

Spermatogenesis is a developmental process of proliferation and differentiation, and it was divided into mitosis, meiosis and spermiogenesis, Spermiogenesis, an important step required to produce sperm of species-specific nuclear shapes, undergo dramatic morphological changes-for example, formation of acrosome, chromatin condensation, nuclear shaping and appearance of sperm tail. Defects in sperm development can cause various types of teratozoospermia(e.g. globozoospermia or macrozoospermia). The role of spermatozoa is to fertilize eggs to continue life as a species, however, teratozoospermia is generally relevant to clinical male infertility.In our previous work, we identified a series of up-regulated and down-regulated genes which represented in a gradually increased or decreased manner in the developmental stages of mice testis using Affymetrix Genechip mouse microarrays. According to nomenclature of the HUGO Gene Nomenclature Committee(HGNC), we termed a novel gene as Spata46(Spermatogenesis associated 46) which is also known as 1700015E13 Rik and C1ORF111. We proved that Spata46 was expressed exclusively in mouse testis in an age-dependent manner by RT-PCR and RT-qPCR. Though immunofluorescence and cell experiment, we found that SPATA46 had a specific localization restricted to subacrosomal area of condensed spermatids and it was located at nuclear membrane with a transmembrane region on N-terminal of the protein.Furthermore, we demonstrated that a deletion of Spata46 was responsible for male mouse subfertility, and the cause of subfertility was characterized by abnormal sperm head shapes and a failure of sperm-egg fusion. At the subcellular level, SPATA46-deficient condensed spermatids displayed structural defects of discontinuous nuclear envelope and a cavity in the nuclear associated with abnormal nuclear shaping. Meanwhile, in vitro, we found that the absence of SPATA46 led to accumulation of sperm around perivitelline space of the eggs, suggesting functional relevance of SPATA46 for sperm-egg fusion.Taken together, these results indicated that SPATA46 was a novel protein involved in the sperm head reshaping and the sperm-egg fusion.