Deletion of Spata2 by CRISPR/Cas9n causes increased inhibin alpha expression and attenuated fertility in male mice†

As somatic cells in the testis seminiferous tubule, Sertoli cells provide the medium for spermatogenesis. One of the important functions of Sertoli cells is synthesizing and secreting cell factors to affect the production of sperm; however, much of those molecular regulation mechanisms remain unknown. Here, we confirm the localization of protein SPATA2 (spermatogenesis-associated protein 2), which had previously been shown to be highly expressed in Sertoli cells of the adult mouse testis. To further conduct a functional study, we generated SPATA2 global knockout mice via use of the CRISPR/Cas9n gene editing technology. The 120-day-old knockout mice testes showed almost a 40% decrease in size and weight and variations in the histomorphology of the seminiferous epithelium, with a 40% decrease in sperm count. Further examination revealed that the proliferation of germ cells in the seminiferous tubules was attenuated by 28%. In addition, we found that SPATA2 deletion led to an approximately 70% increase in the inhibin alpha-subunit mRNA and protein level in the testes compared to that of wild-type mice. Our data revealed the impact of SPATA2 on male fertility and suggested that SPATA2 ensures the normal secretory function of Sertoli cells.