Upon fusion of sperm and oocyte at fertilization, a series of events is initiated whereby the highly compacted sperm nucleus expands and is transformed into a male pronucleus capable of DNA synthesis. The regulation of these early post-fusion fertilization events has been studied using in vitro fertilization and sperm microinjection methods. It was learned that the first step in reactivation of the mammalian sperm nucleus is reduction of sperm protamine disulfide bonds by the oocyte. This step is modulated by glutathione, the levels of which increase during oocyte maturation and correlate with the relative sperm decondensing activity of oocytes at different developmental stages. Once sufficient protamine disulfide bonds have been released, the sperm chromatin becomes accessible to oocyte factors that induce its decondensation, which is dependent upon the type of protamine present, a species specific characteristic.