Testis-Specific Serine Kinase (TSSK) Proteins Family in Male Fertility and as Targets for Non-hormonal Male Contraception.

Male contraception is a very active area of research. Several hormonal agents have entered clinical trials, while potential non-hormonal targets have been brought to light more recently and are at earlier stages of development. The general strategy is to target genes along the molecular pathways of sperm production, maturation or function, and it is predicted that these novel approach will hopefully lead to more selective male contraceptive compounds with a decreased side-effect burden. Protein kinases are known to play a major role in signaling events associated with sperm differentiation and function. In this review, we focus our analysis on the Testis-Specific Serine Kinase (TSSK) proteins family. We have previously shown that members of the family of TSSKs are postmeiotically expressed in male germ cells and in mature mammalian sperm. The restricted postmeiotic expression of TSSKs as well as the importance of phosphorylation in signaling processes strongly suggests that TSSKs have an important role in germ cell differentiation and/or sperm function. This prediction has been supported by the reported sterile phenotype of the Tssk6 knock-out (KO) mice and of the double Tssk1 and Tssk2 KO mice, and by the male subfertile phenotype observed in a Tssk4 KO mouse model. The established role of TSSKs in spermiogenesis and in male fertility, together with their unique kinase features, strongly supports this family of protein kinases as a very promising drug-discovery target for development of a non-hormonal male contraceptive.