The effect of sodium hydrogen carbonate(NaHCO3)on human sperm adenylyl cyclase activity

2021-11-27 21:16AliAhmadi
Precision Medicine Research 2021年1期

Ali Ahmadi

1Department of Biological Sciences and Technologies,Islamic Azad University Sari Branch,Sari,Iran.

Sperm fertility and motility requires the presence of a functional flagellum to act as a motor to enable sperms to move in fluids.Cyclic adenosine monophosphate(cAMP),as a regulator of many biological pathways,contributes in mammalian sperms to the production of soluble adenyl cyclase,a process which is regulated through Ca2+and HCO3-dependent mechanisms and triggers widespread physiological alterations essential to sperm viability.The aim of this study was to investigate the effect of sodium hydrogen carbonate(NaHCO3)on human sperm adenylyl cyclase activity.Studies show that flagellum is essential for sperms to keep their motility.Furthermore,multiple cellular and molecular players and pathways(i.e.,capacitance)are critical for normal maturation of sperms in final stages[1].Sperm capacity is an incorrect maturation process observed in the female reproductive system or can be tested in specific environments,the end point of which has been shown to allow the sperm to withstand the acrosome reaction and fertilize the egg.Interactions between membrane components(e.g.,ion channels)and intracellular skeletal proteins are strictly regulated and are important for promoting these signaling pathways.Carriers can disrupt or regulate the function of these proteins,which can lead to impaired ciliary motility.This in turn is known as a trigger of infertility.Several studies in animal models have shown that mammalian sperm motility is,atleastin part,dependent on cAMP-derived signaling pathways[2].The role of NaHCO3,and not cytoplasm pH,in determining sperm motility hasbeen suggested.Adenylyl cyclase is as enzyme which has been involved in regulating the level of NaHCO3in sperms of mammalians,which in turn its activity is dependent on Ca2+concentration.NaHCO3and Ca2+are factors that appear to be required for capacitors,and in addition,changes in adenylyl cyclase and cAMP activity in some species have been hypothesized to play a role in capacity building[3].Ultra-microscopy and electrophysiology advancementsnow provide opportunities to effectively study mammalian parasites.On the other hand,studies are conducted on flagellar ion channels and transporters that are involved in maintaining proton,calcium,potassium,and sodium intracellular concentrations.It is important to precisely recognize the molecular and cellular players participating in the determination of sperm motility.This is essential to improve the diagnosis of male infertility.

The HCO3-in the structure of NaHCO3seems to have an essential role in regulating the activity of sperm adenyl cyclase.It has been revealed that replacing NaHCO3with NaClhasdeviated the regulating role of this compound on the enzyme activity.On the other hand,cyclic AMP analogs can replace the bicarbonate anion in support of phosphorylation of tyrosine and capacitor proteins,as previously shown.Furthermore,pH alteration in the range of 7 to 8 showed no significant impact on the activity of this enzyme; instead, adenylyl cyclase-dependent protein phosphorylation was promoted in the presence of NaHCO3[4].

The role of external factors regulating intracellular events through modulating secondary messengers and receptors have been suggested in governing cellular and molecular interactions in sperm [1].The accomplishment of capacity cellular events in mammalian sperm;however,isalso underthe regulation of some sperms’intrinsic factors.Although the precise role of these inherent regulators is unclear,these seem to be the main regulators governing sperm plasma membrane function,and changes in membrane properties that may lead to pre-programmed cell neutralization.These changes are considered to be fundamental for the creation of the capacitive stare[5].In a previous report,the development of a capacitive state in toxic epididymal sperm was investigated by assessing the capability of sperms in acquiring the B-pattern of chlorotracyline fluorescence to tolerate the ZP-induced acrosome reaction to fertilize metaphase II.In vitro conditions together with protein tyrosine phosphorylation are performed as a specific subset of sperm proteins[6].The presence of NaHCO3,Ca2+,and albumin in the culture medium was essential for the start of both capacitors and tyrosine protein phosphorylation.These findings indicate the role of NaHCO3in tyrosine phosphorylation of proteins and the fact that these specific ions are involved in regulating mammalian cAMP metabolism.Also,capacity-dependent changes in tyrosine protein phosphorylation showed that the presence of HCO3-,Ca2+,and bovine serum albumin was dispensable.Also,the activity of adenylyl cyclase was showed to be dependent on the presence of HCO3-in the structure of NaHCO3,because its replacement with NaCl has been shown to have no effects on the enzyme activity[7].In addition,the effect of NaHCCl3on enzyme activity as a result of pH change Because the pH adjustment of the enzymes used in the enzyme from pH 7–8 has not been shown to have any effect on the enzyme activity[8].

In this study recent developments in ion channel function and transport and corresponding signaling pathways in mammalian sperm flagella have been shown.

In summary,adenylyl cyclase enzymes(ACs)are categorized into two transmembrane(tmAC)and soluble(sAC or SACY)types.The first class(i.e.,tACs)is under the regulation of heterothromeric G proteins,while the second type is under the influence of bicarbonate and Ca2+.Accordingly,SACY in mammalian sperm contribute an essential role in the synthesis of cAMP.This enzyme is also regulated by HCO3-and Ca2+dependent pathways and finally trigger the cAMP-dependent cellular and molecular events involved in the sperm capacitor.However,it is not established if tAC is expressed in mammalian sperms; besides, their precise role in sperm development is yet to be divulged.Various factors,including Ca2+and HCO3-,also have been reported to regulate mammalian sperm motility[7,9].