Male infertility is a global issue caused by poor sperm quality,particularly motility.Enhancement of the sperm quality may improve the fertilization rate in assisted reproductive technology(ART)treatment.Scriptaid,wit...Male infertility is a global issue caused by poor sperm quality,particularly motility.Enhancement of the sperm quality may improve the fertilization rate in assisted reproductive technology(ART)treatment.Scriptaid,with a novel human sperm motility-stimulating activity,has been investigated as a prospective agent for improving sperm quality and fertilization rate in ART.We evaluated the effects of Scriptaid on asthenozoospermic(AZS)semen,including its impact on motility stimulation and protective effects on cryopreservation and duration of motility,by computer-aided sperm analysis(CASA).Sperm quality improvement by Scriptaid was characterized by increased hyaluronan-binding activity,tyrosine phosphorylation,adenosine triphosphate(ATP)concentration,mitochondrial membrane potential,and an ameliorated AZS fertilization rate in clinical intracytoplasmic sperm injection(ICSI)experiments.Furthermore,our identification of active Scriptaid analogs and different metabolites induced by Scriptaid in spermatozoa lays a solid foundation for the future biomechanical exploration of sperm function.In summary,Scriptaid is a potential candidate for the treatment of male infertility in vitro as it improves sperm quality,prolongs sperm viability,and increases the fertilization rate.展开更多
Although the somatic cell nuclear transfer(SCNT) technique has been used extensively for cloning and generating transgenic pigs,the cloning efficiency is still very low.It has been proposed that the low efficiency of ...Although the somatic cell nuclear transfer(SCNT) technique has been used extensively for cloning and generating transgenic pigs,the cloning efficiency is still very low.It has been proposed that the low efficiency of this technique is the result of incomplete epigenetic reprogramming and abnormal gene expression during early embryonic development.In this study,we investigate the effect of Scriptaid,a low-toxicity histone deacetylase inhibitor,on the developmental competence of porcine SCNT embryos.We found that treating SCNT embryos with 500 nmol/L Scriptaid for 15 h after activation significantly enhanced the blastocyst formation rate(27.7%) compared with the untreated group(control)(12.2%,P<0.05).Using an immunofluorescence technique to measure the average fluorescence intensity,we also found that treating SCNT embryos with Scriptaid increased the level of histone acetylation on histone H3 at lysine 14(acH3K14).Furthermore,treating embryos with Scriptaid increased the expression level of three genes that play important roles during embryonic development(Oct4,Klf4 at the blastocyst stage and Nanog at the 4-cell stage).Moreover,the expression level of the apoptosis-related gene Caspase-3 was significantly lower in the Scriptaid-treated SCNT embryos compared with the control SCNT embryos at the 4-cell and blastocyst stages.In conclusion,these results indicate that Scriptaid treatment improves the development and nuclear reprogramming of porcine SCNT embryos.展开更多
文摘Male infertility is a global issue caused by poor sperm quality,particularly motility.Enhancement of the sperm quality may improve the fertilization rate in assisted reproductive technology(ART)treatment.Scriptaid,with a novel human sperm motility-stimulating activity,has been investigated as a prospective agent for improving sperm quality and fertilization rate in ART.We evaluated the effects of Scriptaid on asthenozoospermic(AZS)semen,including its impact on motility stimulation and protective effects on cryopreservation and duration of motility,by computer-aided sperm analysis(CASA).Sperm quality improvement by Scriptaid was characterized by increased hyaluronan-binding activity,tyrosine phosphorylation,adenosine triphosphate(ATP)concentration,mitochondrial membrane potential,and an ameliorated AZS fertilization rate in clinical intracytoplasmic sperm injection(ICSI)experiments.Furthermore,our identification of active Scriptaid analogs and different metabolites induced by Scriptaid in spermatozoa lays a solid foundation for the future biomechanical exploration of sperm function.In summary,Scriptaid is a potential candidate for the treatment of male infertility in vitro as it improves sperm quality,prolongs sperm viability,and increases the fertilization rate.
基金supported by the National Basic Research Program of China(2009CB941000)
文摘Although the somatic cell nuclear transfer(SCNT) technique has been used extensively for cloning and generating transgenic pigs,the cloning efficiency is still very low.It has been proposed that the low efficiency of this technique is the result of incomplete epigenetic reprogramming and abnormal gene expression during early embryonic development.In this study,we investigate the effect of Scriptaid,a low-toxicity histone deacetylase inhibitor,on the developmental competence of porcine SCNT embryos.We found that treating SCNT embryos with 500 nmol/L Scriptaid for 15 h after activation significantly enhanced the blastocyst formation rate(27.7%) compared with the untreated group(control)(12.2%,P<0.05).Using an immunofluorescence technique to measure the average fluorescence intensity,we also found that treating SCNT embryos with Scriptaid increased the level of histone acetylation on histone H3 at lysine 14(acH3K14).Furthermore,treating embryos with Scriptaid increased the expression level of three genes that play important roles during embryonic development(Oct4,Klf4 at the blastocyst stage and Nanog at the 4-cell stage).Moreover,the expression level of the apoptosis-related gene Caspase-3 was significantly lower in the Scriptaid-treated SCNT embryos compared with the control SCNT embryos at the 4-cell and blastocyst stages.In conclusion,these results indicate that Scriptaid treatment improves the development and nuclear reprogramming of porcine SCNT embryos.
