The Sperm‐Associated Antigen 11A (Spag11a) Knockout Mice Display Sub‐Fertility and Perturbations in the Sperm Proteome.

Spermatogenesis and sperm maturation that occur in the testis and epididymis respectively are crucial for fertility. Factors secreted by the testicular and epididymal epithelial cells govern the processes of gametogenesis and maturation. Proteins encoded by the sperm‐associated antigen 11a (Spag11a) gene are implicated as having a possible role in sperm maturation. However, studies that demonstrate their definite role in fertility and sperm function using knockout models have not yet reported. In this study, Spag11a knockout mice were generated, genotyped and the reproductive parameters (fecundity, sperm count, capacitation, and acrosome reaction) and sperm proteome were determined. Litter size and sperm count were decreased in the Spag11a knockout mice when compared to the wild‐type controls. Spermatozoa from the knockout mice were able to undergo capacitation. However, acrosome reaction did not occur in sperm obtained from knockout mice. Structural abnormalities in the head and tail structures were evident in the spermatozoa of knockout mice. Perturbations in the expression of sperm proteins that are involved in gametogenesis were evident. The subfertility observed in Spag11a knockout mice could be a manifestation of lower sperm count, impaired acrosome reactions, and disturbances in the sperm proteome. The results of this study lend further support to the role of Spag11a gene in male gamete function. Summary: Analyzing the role of male reproductive tract‐specific proteins in male fertility using knockout models is an active area of investigation. Although a large number of knockout models for genes that are specific to the testis are generated and the reproductive function studied, there are very few studies that analyze the role of epididymal proteins that contribute to sperm function and fecundity. In this study, the effect of knockout of an epididymal‐specific gene, Spag11a, on male reproductive function, especially the fecundity, capacitation, acrosome reaction, and sperm proteome was analyzed. Our observations indicate subfertility and compromised sperm function associated with perturbations in sperm proteome. Using shRNA‐mediated Spag11a mRNA ablation and active immunization‐mediated SPAG11A protein ablation, we previously demonstrated the possible role of Spag11a in sperm function and fecundity. This study significantly differs from our previous studies because we used a higher level of gene ablation model, that is, the Spag11a knockout mice to provide further evidence. Furthermore, we also analyzed the molecular changes at the proteome level under conditions of Spag11a gene knockout. Thus, this study carried a lot of significance since it reiterates the observations made in our previous studies using an animal model that truly reflects the ablation of Spag11a expression. [ABSTRACT FROM AUTHOR]