Functional activity of adenylyl and guanylyl cyclases in human spermatozoa with different motility

Abstract

The most important functional characteristics of ejaculated spermatozoa is their ability to directional sustained movement that to a large extent determines their fertility. It is assumed that the enzymes with cyclase activity--adenylyl cyclase (AC) and guanylyl cyclase (GC), soluble and membrane-bound forms of which are found in human and mammalian sperm, play a key role in the regulation of motility. However, the functional activity of the cyclases in ejaculated spermatozoa with different motility and their contribution to the regulation of this process is virtually unexplored. The aim of this work was the functional characteristics of AC and GC in human sperm ejaculates with different content of motile forms of spermatozoa, and the study of regulation of these enzymes by hormones and non-hormonal agents. We found the differences in the activity and regulatory properties of AC and GC in the ejaculates differing in the content of motile forms of sperm. The basal AC activity and its sensitivity to bicarbonate anion and manganese cations, activators of cytosolic AC (cAC), were increased in ejaculates with a high proportion of motile spermatozoa. At the same time, AC effect of forskolin, GppNHp and adrenergic receptor agonists acting via membrane-bound AC (mAC) were significantly reduced in this case. Cytosolic GC in the ejaculates with a high proportion of motile spermatozoa was more sensitive to manganese cations, but the basal activity of GCs was altered slightly. The increase in the content of motile spermatozoa in the ejaculates led to decrease in the sensitivity of receptor GC to CNP, while the sensitivity to ANP was maintained, which indicated a change in the pattern of enzyme regulation with natriuretic peptides in favor of ANP, an important regulator of sperm chemotaxis. Thus, we have concluded that the change in the proportion of motile spermatozoa in the ejaculate induces changes in the functional activity and regulatory properties of soluble and membrane-bound forms of AC and GC, which can be used to control the motility, chemotaxis, acrosomal reaction and other processes determining the fertility of male germ cells.