“…Mature spermatozoa cannot fertilize oocytes even if they are motile and physiologically normal . In internally fertilizing animals, mature spermatozoa achieve fertilization competence only after they enter the female genital tract; the alterations of spermatozoa once inside the tract is known as capacitation. , Only capacitated spermatozoa can undergo the acrosome reaction upon binding to the zona pellucida, at which point they become capable of penetrating and fertilizing an egg. − Capacitation confers a series of metabolic and structural modifications to the spermatozoa that are accompanied by changes in membrane fluidity; HCO –3 , Ca 2+ , and cAMP levels; PKA activity; and tyrosine phosphorylation of proteins. ,,,− Studies have demonstrated that tyrosine phosphorylation is upregulated during capacitation. − Other studies have consistently reported a positive correlation between capacitation and protein tyrosine phosphorylation in various mammalian species, including humans, that is correlated with fertilization and male fertility. ,,,− The relationship between capacitation and tyrosine phosphorylation was discovered before the beginning of the 21st century; however, the basic molecular mechanism underlying tyrosine phosphorylation-mediated control of capacitation, the acrosome reaction, and male fertility is still unclear. Our review of the literature showed that four major signaling pathways modulating tyrosine phosphorylation-guided capacitation and the acrosome reaction have been reported, namely the cAMP/PKA-dependent pathway, − ,− receptor tyrosine kinase pathway, , nonreceptor protein tyrosine kinase pathway, and G-protein coupled receptor pathway. − The cAMP/PKA-dependent pathway is the most extensively studied and is more specific to sperm cells; therefore, we discuss in detail the relationship of this pathway with tyrosine phosphorylation, male fertilization, and embryonic development (depicted hypothetically in Figure )…”