Cyclic AMP Signalling During Mammalian Sperm Capacitation – Still Largely Terra Incognita

Cyclic AMP is known to play a major role in intracellular signalling during mammalian sperm capacitation. However, despite much research, many of the molecular details of cyclic AMP's involvement remain obscure. In this review, I discuss the following aspects, presenting some original data as illustration where relevant. With respect to cyclic AMP synthesis, uncertainties exist as to the number of forms of adenylyl cyclase that are present in the spermatozoon, whether they are cytosolic or bound to subcellular structures, and which physiological effectors they respond to (e.g. bicarbonate, Ca²⁺, or receptor‐coupled G‐proteins). While net intracellular levels of cyclic AMP in spermatozoa depend upon the relative activities of adenylyl cyclase and phosphodiesterase, there are wide between‐sample variations within species, both in basal levels and in levels attained after activation of the cyclase (e.g. after sperm treatment with bicarbonate). Moreover, minor changes in bulk cyclic AMP levels can result in large changes in cyclic AMP‐dependent functions. Finally, while cyclic AMP levels respond very rapidly to sperm treatment by effectors such as bicarbonate and Ca²⁺ (key components of capacitating media), there are big discrepancies between the rates of functional response. For example, enhancement of motility and collapse of phospholipid asymmetry take place within a few minutes, whereas more than 1 h of exposure to capacitating conditions is needed for cyclic AMP‐dependent protein tyrosine phosphorylation to become detectable or for the sperm population to attain a capacitated state.