Ed to undergo the acrosome reaction when EPAC was reacted with certain blocking antibodies and that the cellpermeable EPACselective cAMP analog induced the acrosome reaction. Kinukawa et al. [90] reported the cAMPdependent activation from the Epac2Rap2 signaling cascades regulating the conversion of microtubule sliding into flagellar bending in hamster epididymal spermatozoa. Furthermore, MiroMoran et al. [91] reported that an immunodetection signal of EPAC1 was observed within the marginal segment in the acrosome and middle piece of boar spermatozoa and that RAP1 and Ecadherin may well be cAMPEPAC1 signaling molecules. In addition, details on other elements in the intracellular cAMP signal transduction in mammalian spermatozoa are readily available in a preceding evaluation [92].Acrosome ReactionThe mammalian spermatozoon is structurally composed of a head, neck (connecting piece) and flagellum. The head is divided into two components, the acrosomal and postacrosomal regions, according to lightmicroscopic traits. The former area is additional divided into 3 domains, the marginal, principal and equatorial segments. The marginal and principal segments are collectively termed the acrosomal cap [93]. The acrosome reaction will be the exocytosis from the acrosomal contents following numerous partial fusions between the plasma and outer acrosomal membranes. It’s apparently triggered by an increase in intracellular Ca2, which can be recruited from the extracellular space too as the internal retailer (outer acrosomal membrane) through cation channels, including the voltageoperated Ca2 channels (VOCCs), inositol triphosphate receptor (IP3R) and storeoperated channels (SOCs). Recently, the group research of Darszon and Visconti indicates that acrosome reactioninducible Ca2 entry into mouse spermatozoa is mediated primarily via VOCCs, that are activated by membrane possible hyperpolarization throughout capacitation [94]. For the last many decades, it has been believed that a particular zona pellucida glycoprotein (ZP3 of mouse oocytes) has dual functions as a specific spermbinding web site (sperm receptor) plus a physiological inducer from the acrosome reaction [95]. Nevertheless, Gahlay et al. [96] claimed that another zona pellucida glycoprotein (ZP2), as an alternative to ZP3, was pivotally involved in the sperm binding for the zona pellucida in mice. Jin et al. [97] observed applying a video microscopic in vitro fertilization system that mouse spermatozoa underwent the acrosome reaction ahead of contact together with the zona pellucida and then fertilized oocytes. In addition, spermatozoa with an intact acrosome barely initiated the reaction on the zona pellucida. These findings strongly need reexamination on the roles in the zona pellucida glycoprotein within the acrosome reaction. Alternatively, it need to be noted that progesterone (included by the cumulus oophorus) can stimulate Ca2 entry in the extracellular milieu [98], which activates the cAMPEPACsmall Gprotein (RAP1 and RAB3A) signaling cascades then the SNAREdependent mechanism, major to the acrosome reaction in human spermatozoa [88, 89]. Effects of this steroid on the acrosome reaction happen to be reported to become mediated nongenomically by the exceptional receptors around the plasma membrane in numerous Nalfurafine GPCR/G Protein species [42, 9902]. The involvement of the cAMP signal transduction within the acrosome reaction can also be supported by study with boar spermatozoa displaying that treatment using a cellpermeable cAMP analog can induce the acrosome reaction immediately after the capacitationassocia.