Abstract: The present invention relates to methods of decreasing sperm production in a male mammal by administering an effective amount of SHP2 inhibitor to decrease the spermatogonial stem cell (SSC) population. In particular non-limiting embodiments, this method may be used to achieve sterilization. The invention is based, at least in part, on studies in mice which show that (i) in the absence of SHP2, spermatogenesis is blocked at an initial step because spermatogonia cannot be produced from SSCs and (ii) global knock out of SHP2 inhibits the release of mature spermatozoa and causes premature release of germ cells as well as defects in the orientation and migration of elongated spermatids. In certain non-limiting embodiments, the invention provides for a method of decreasing fertility in a male human by administering an effective amount of a SHP2 inhibitor.