Figure 1: Schematic representation of pathways believed of being involved in the regulation of mammalian sperm motility. Activation of a Na+/HCO3− (NBC) co-transporter and the regulation of HCO3−/Cl− by SLC26 transporters increase HCO3− levels. The activation of the sperm Na+/H+ exchanger (sNHE) aligned with the activation of the proton channel (Hv1) leads to a raise of the pHi, which activates CatSper, a cation channel of sperm that enables the entry of Ca2+ and thus increases the internal Ca2+ concentration ([Ca2+]). Progesterone, a steroid hormone synthesized by the cumulus/granulosa cells, activates CatSper either by binding to the channel itself or to an associated protein. Further, albumin, the main protein of human blood plasma and oocyte glycoproteins, together with alkalinization of the sperm cytoplasm also, elevates the internal [Ca2+]., The overall Ca2+ increase may influence glycolysis and the axoneme activity promoting hyperactivation of motility.  Further, HCO3− and Ca2+ regulate the atypical soluble adenylyl cyclase (sAC), which generates cAMP and that by its turn activates protein kinase A (PKA). PKA induces phosphorylation of axonemal dynein, leading to consumption of ATP and thus increases the pHi . PKA activates sperm tyrosine kinases (with serine and threonine residues) to trigger a cascade of protein phosphorylation involved in sperm motility.,, Increased cAMP may activate PKA that in turn activates tyrosine kinase and seems to inhibit tyrosine phosphatase. The Ca2+ levels are regulated by a plasma membrane Ca2+ -ATPase pump (PMCA4), expressed in the principal piece of the axoneme, which extrudes Ca2+ and is essential for hyperactivated motility and male fertility.