Development of male contraceptive through manipulation of CaS

The project is aimed at developing male contraceptives on a collaborative basis between the Institute of Basic Medical Sciences (project leader Bjørn Steen Skålhegg) and the Department of Andrology, The National University Hospital of Norway (research lea der Dr. Peter Fedorcsak and head of department Dr. Tom Tanbo). We have made a unique discovery in that we have identified and characterized the function of the gene and the protein for CaS. CaS is a catalytic subunit of the protein kinase A (PKA) family of serine (Ser) and threonine (Thr) protein kinases and is only expressed (identified) one place in the body, namely the sperm cell. We and others have shown using knock-out (KO) mice that CaS regulates sperm cell forward velocity and male fertility. This conclusion is based on to experiments performed on sperm cells isolated from CaS KO mice which are unable to penetrate the egg due to abrogated swimming capability. Moreover, breeding experiments with such mice demonstrate that 100 % of the male mice KO for CaS are infertile. Our experiments demonstrate target validation of CaS as a unique molecule that can be manipulated by substances (leads) that can be used to develop male contraceptives. Due to the unique location of CaS and its function (one target , one place, one function) our discovery is rare both in a national and international perspective. Substances that can target CaS? function are expected to be used pharmacologically to regulate sperm movement without side effects.