Cyclic adenosine 3',5'-monophosphate (cAMP), the first second messenger to be 
described, plays a central role in cell signaling in a wide variety of cell 
types. Over the last decades, a wide body of literature addressed the different 
roles of cAMP in cell physiology, mainly in response to neurotransmitters and 
hormones. cAMP is synthesized by a wide variety of adenylyl cyclases that can 
generally be grouped in two types: transmembrane adenylyl cyclase and soluble 
adenylyl cyclases. In particular, several aspects of sperm physiology are 
regulated by cAMP produced by a single atypical adenylyl cyclase (Adcy10, aka 
sAC, SACY). The signature that identifies sAC among other ACs, is their direct 
stimulation by bicarbonate. The essential nature of cAMP in sperm function has 
been demonstrated using gain of function as well as loss of function approaches. 
This review unifies state of the art knowledge of the role of cAMP and those 
enzymes involved in cAMP signaling pathways required for the acquisition of 
fertilizing capacity of mammalian sperm. This article is part of a Special Issue 
entitled: The role of soluble adenylyl cyclase in health and disease.