cAMP and the Fibrous Sheath Protein CABYR (Ca2+-Binding Tyrosine-Phosphorylation-Regulated Protein) Is Required for 4D Sperm Movement

Abstract

A new life starts with successful fertilization whereby one sperm from a pool of millions fertilizes the oocyte. Sperm motility is one key factor for this selection process, which depends on a coordinated flagellar movement. The flagellar beat cycle is regulated by Ca2+ entry via CatSper, cAMP, Mg2+, ADP and ATP. This study characterizes the effects of these parameters for 4D sperm motility, especially for flagellar movement and the conserved clockwise (CW) path chirality of murine sperm. Therefore, we use detergent-extracted mouse sperm and digital holographic microscopy (DHM) to show that a balanced ratio of ATP to Mg2+ in addition with 18 µM cAMP and 1 mM ADP is necessary for controlled flagellar movement, induction of rolling along the long axis and CW path chirality. Rolling along the sperm’s long axis, a proposed mechanism for sperm selection, is absent in sea urchin sperm, lacking flagellar fibrous sheath (FS) and outer-dense fibers (ODFs). In sperm lacking CABYR, a Ca2+-binding tyrosine-phosphorylation regulated protein located in the FS, the swim path chirality is preserved. We conclude that specific concentrations of ATP, ADP, cAMP and Mg2+ as well as a functional CABYR play an important role for sperm motility especially for path chirality.

Liraglutide improved the reproductive function of obese mice by upregulating the testicular AC3/cAMP/PKA pathway

“…As an important secondary messenger, it regulates various signaling pathways and is crucial for regulating sperm motility, maturation, and capacitation. Both cAMP and its targeted receptors regulate various signaling pathways, including intracellular pH increase and protein tyrosine phosphorylation, which in turn regulate capacitation processes and acrosome reactions [ 41 ]. The pH within male germ cells plays a vital role in sperm motility, and the sodium-hydrogen exchanger NHE primarily maintains the intracellular pH balance.…”

“…During capacitation, the increase in cAMP activates cAMP-dependent PKA, resulting in the phosphorylation of a large amount of sperm protein, especially the axoneme protein, by PKA, leading to the induction of flagellar motility. Modifying protein structure and function promotes the completion of a large amount of sperm maturation [ 41 , 43 ]. Recent studies have confirmed the central role of cAMP in regulating sperm movement through flagellar movement and velocity analysis.…”

“…Recent studies have confirmed the central role of cAMP in regulating sperm movement through flagellar movement and velocity analysis. cAMP is a prerequisite for inducing lateral head displacement and flagellar movement in the XY and Z planes, resulting in an increase in swimming speed [ 41 ]. In vitro studies have shown that when PKA-Cα is defective, in addition to motor defects, it also exacerbates sperm head distortion [ 43 ].…”