Alternatively, NADPH has been postulated to be a cofactor for a putative NADPH oxidase that would be responsible for the production of ROS in human sperm. One of these ROS, H2O2, exerts a physiological function in controlling the levels of protein tyrosine phosphorylation. In the mouse, the phosphorylation of tyrosine residues is important for sperm functions such as capacitation and acrosome reaction. In addition, glucose has been shown to inhibit tyrosine phosphorylation during capacitation of bovine sperm. In mouse spermatozoa, glucose may exert indirect control of protein tyrosine phosphorylation of the sperm, after its metabolism through the PPP and the concomitant production of NADPH.
In conclusion, it appears that the beneficial effect of glucose on gamete fusion is probably mediated by its metabolism through the PPP of the spermatozoa, which we have shown to be functional. The ability of capacitated sperm to fuse with the oocyte is lost after removal of glucose or PPP inhibition by cytochalasin B and is restored by the addition of glucose or NADPH. This suggests the existence of an event in spermatozoa that is linked to gamete fusion and controlled by glucose via the production of NADPH, although the key functions that depend on NADPH remain to be defined.