Sperm Morphological And Functional Modification By Synthetic Acrosin Inhibitor

OBJECTIVE:No male contraceptive drugs are applicable today.Indeed, many scientists focus their interest in this field.It is well known that sperm acrosome reaction and acrosin enzyme release are necessary for fertilization. This study is to evaluate if synthetic acrosin inhibitor may affect sperm acrosin.METHOD:1.Establishment of selection model based on acrosin inhibition ability:Synthesized a series of acrosin inhibitors.The inhibition effect of acrosin inhibitors on sperm acrosin was analyzed by improved Kennedy assay.2.Morphological analysis and Hemi-zona assay:After treated by acrosin inhibitors,sperm morphological modification was observed by electron microscope.Sperm penetration ability was evaluated by Hemi-zona assay:Colletion of unfertilized oocytes,Micro-dissection of one zona pellacide(ZP) in 2,count the number of sperm which penetrated ZP after 4h incubation.3.In vivo rat test:Feed male rats(n=40) with synthetic acrosin inhibitors during till 7 weeks,sperm acrosin activity and serum FSH,LH,T level were monited.RESULT:1.It was observed that 4M-2434 and GS-0122 are two most efficiency sperm acrosin inhibitors,all enzyme activity of 7.5×10~6 sperm was totally inhibited at 0.9μmol/mL,2μmol/mL,respectively.2.The penetrating number of sperm was negatively correlated with the concentration of 4M-2434 and GS-0122.There was no sperm penetration at 0.9μmol/mL and 2.0μmol/mL,respectively.3.Feed with 4M-2434 and GS-0122 in 7 weeks,a negative correlation with acrosin enzyme activity in rats was obtained(P＜0.05).There is no modification of serum FSH,LH,T level and sexual organ weight.CONCLUSION:These results indicate that computer assisted synthesization of acrossin inhibitor is applicable,4M-2434 and GS-0122 are two acrossin inhibitors with most efficiency.Further evaluations are necessary for its male contraceptive potency.