User:Yzha326/sandbox

Mechanisms
''Mammalian sperm cells become more active when they approach an egg cell in a process called sperm activation. Sperm activation has been shown to be caused by calcium ionophores in vitro, progesterone released by nearby cumulus cells and binding to ZP3 of the zona pellucida'', as well as Increase tyrosine phosphorylation in sperm

''The initial change is called "hyperactivation", which causes a change in spermatozoa motility. They swim faster and their tail movements become more forceful and erratic.''

''wA recent discovery links hyperactivation to a sudden influx of calcium ion into the tails. The whip-like tail (flagellum) of the sperm is studded with ion channels formed by proteins called CatSper,''which are exclusive to male sperm cells. . These channels are selective for calcium ions, however, if Calcium is absent, sodium can also move through CatSper channels into sperm. CatSper channels need to remain open for spermatozoa to maintain the state of hyperactivation. ''The sudden rise in calcium levels causes the flagellum to form deeper bends, propelling the sperm more forcefully through the viscous environment. Sperm hyperactivity is necessary for breaking through two physical barriers that protect the egg from fertilization''

Progesterone
Progesterone is the most abundant hormonal chemo-attractant that affect hyperactivation of sperm. The effects occur in two stages: flagellar arrest when first exposed to progesterone, followed by hyperactivation. In a temporal gradient of progesterone, sperm exhibit increased hyperactivation, which results in fluctuation in direction and velocity; in a spatial gradient of progesterone, sperm exhibit decreased hyperactivation due to the continuous stimulation that cause sperm to maintain its flagellar arrest state. In a spatial gradient, sperm will travel straight throughout the gradient with a few or zero episodes of hyperactivation.

Temperature
Sperm experience heat induced hyperactivation when the spermatozoa temperature reaches 40°C and sustains for 10-15 minutes. There are seven heat shock protein (HSP70-HSP90) known to be contributing factors, these proteins activate transcription of enzymes that phosphorylates essential enzymes (mainly tyrosine), tyrosine residue in flagellum can directly induce and control hyperactivated motility;  other effect of heat induced hyperactivation is to activate DNA gyrase, which combines with DNA topoisomerase to catalyze DNA relaxation activity in cells.

cAMP and Bicarbonate
cAMP activates PKA which triggers cascade of phosphorylation of serine and theonine of proteins, ultimately phosphorylates tyrosine residues in the flagellum. cAMP is produced by adenylyl cyclase (ADCY) which converts ATP to cAMP; ADCY activity of spermatozoa is stimulated by HCo3- (Bicarbonate) which corresponds with elevated in vivo pH level. The female reproductive tract gradually increases in pH (higher concentration of HCo3- ) as sperm travel towards ovum; this physiological feature facilitates hyperactivation and ultimately the penetration of zona pellucid.

GABA
Sperm membrane contain many GABA receptors, the binding of GABA has experimentally shown to facilitate hyperactivation.

Synthetic Chemicals
Procaine and 4-aminopyridine are inducer of hyperactivation by increase intracellular storage and influx of calcium. HC-056456 is a reversible blocker of CatSper channel, preventing entry of Calcium or Sodium into sperm, and decrease the rate of hyperactivation.

Importance to fertilization
In 1969, it was first identified that hamster spermatozoa had different motility pattern during the time of fertilization. Since then, this change in motility is defined as hyperactivation. Experiments in both mouse and human spermatozoa have shown significant increase in fertility rate in hyperactivated sperm compare to inactivated ones. Before fertilization, sperm are trapped in viscous medium of epithelial cells of the fallopian tube; hyperactivation give sperm the motility to escape attachment from epithelial cells, and travel upwards guided by chemo-attractants. Hyperactivation is also crucial in the penetration of zona pellucida.

Congenital Dyserythropoietic Anemia Type I (CDA1) is a rare genetic disease of the CDAN1 gene on Chromosome 15 in human. This disorder led to deletion of part of the CDAN1 gene resulting in incomplete and dysfunctional CatSper2 protein and infertility. Individual with CDA1 have abnormal spermatozoa motility, morphology and few hyperactivation episodes.