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Sperm Motility | GeneGlobe

Sperm Motility


Pathway Description

Sperm cells are equipped with a limited repertoire of behaviors that exclusively subserve their purpose to fertilize eggs. The three principal events in sperm mobilization are 1) motility (and chemotaxis) 2) capacitation and 3) the acrosome reaction. When produced in the testis, sperm are immotile; they acquire the ability to swim as they transit through the epididymal tract of mammals. But motility alone is not sufficient to direct a sperm to an egg. The egg itself (or associated structures) must "lure" the sperm by releasing diffusible chemotactic factors. In this regard, intracellular Ca2+, K+, Na+ and Cl- levels also control the waveform asymmetry of sperm flagellar beating and acrosomal reaction. The main physiological inducer of the sperm acrosomal reaction is the zona pellucida. Three sulfated glycoproteins (ZP1, ZP2 and ZP3) principally constitute zona pellucida. ZP3 exhibits most of the sperm binding and acrosomal reaction-inducing activity. The main candidates on sperm membrane that act as primary receptors for ZP3 include Zan and ZPR3.

Capacitation is the most essential process for sperm motility in which adenylate cyclase (AC) and guanylate cyclase (GC) play a prominent role. HCO3 and Ca2+ ions that enter the sperm, activate the soluble form of AC - (sAC), while, female/egg factors stimulate activation of sAC by release of Ca2+ through CatSper. PKA is activated by sAC. Similarly, extracellular cues like ANP and NO activate mGCs and sGCs, respectively to synthesize cGMP. The concomitant increase of both cyclic nucleotides (cAMP and cGMP) leads to a cross-talk between the cAMP and cGMP signaling pathways.

Activation of enzymes like sAC, mGC, sGC and PLC leads to increased generation of the second messengers like cAMP, cGMP, IP3 and DAG. A consequence of the increase of second messengers is the activation of protein kinases such as PKA, PKC and PKG. These kinases in turn facilitate the activation of tyrosine kinases like the PTKs which increase protein phosphorylation; this has an important role in human ZP-induced acrosome reaction. Ca2+-dependent activation of Calm, PLA2 and PLD (with increased generation of other second messengers as arachidonic acid, lysophosphatidylcholine and phosphatidic acid from membrane phospholipids) also contributes to the acrosome reaction. Thus, elevations of sperm Na+, K+, Ca2+, Cl- and H+ together with an increased protein phosphorylation induces signaling pathways that brings about the capacitation and acrosome reaction followed by a wave form asymmetry of motility called hyperactivation, which first occurs during the time of fertilization. Hyperactivation and acrosomal reaction enhances flagellar beating, ultimately resulting in the penetration of outer egg coat and subsequent fertilization of mature ovum.