<abstract>Aim: We describe an approach to search for candidate genes for male infertility using the two human genome databases: the public University of California at Santa Cruz (UCSC) and private Celera databas...<abstract>Aim: We describe an approach to search for candidate genes for male infertility using the two human genome databases: the public University of California at Santa Cruz (UCSC) and private Celera databases which list known and predicted gene sequences and provide related information such as gene function, tissue expression, known mutations and single nucleotide polymorphisms (SNPs). Methods and Results: To demonstrate this in silico research, the following male infertility candidate genes were selected: (1) human BOULE, mutations of which may lead to germ cell arrest at the primary spermatocyte stage, (2) mutations of casein kinase 2 alpha genes which may cause globozoospermia, (3) DMR-N9 which is possibly involved in the spermatogenic defect of myotonic dystrophy and (4) several testes expressed genes at or near the breakpoints of a balanced translocation associated with hypospermatogenesis. We indicate how information derived from the human genome databases can be used to confirm these candidate genes may be pathogenic by studying RNA expression in tissue arrays using in situ hybridization and gene sequencing. Conclusion: The paper explains the new approach to discovering genetic causes of male infertility using information about the human genome.展开更多
We developed tests of sperm-oocyte interaction:sperm-zona binding,zona-induced acrosome reaction,sperm-zona penetration and sperm-oolemma binding,using oocytes which failed to fertilise in clinical in vitro fertilizat...We developed tests of sperm-oocyte interaction:sperm-zona binding,zona-induced acrosome reaction,sperm-zona penetration and sperm-oolemma binding,using oocytes which failed to fertilise in clinical in vitro fertilization(IVF).Although oocyte defects contribute to failure of sperm oocyte interaction,rarely are all oocytes from one wom-an affected.Low or zero fertilization in standard IVFwas usually caused by sperm abnormalities.Poor sperm-zona pel-lucida binding was frequently associated with failure of standard IVF and obvious defects of sperm motility or morpholo-gy.The size and shape of the acrosome is particularly important for sperm binding to the oocyte.The proportion ofacrosome intact sperm in the insemination medium was related to the IVF rote.Inducing the acrosome reaction with acalcium ionophore reduced sperm-zona binding.Blocking acrosome dispersal with an acrosin inhibitor prevented sperm-zona penetration.Sperm-zona penetration was even more highly related to IVF rates than was sperm-zona binding.Some patients had low or zero fertilization rates with standard IVF but normal sperm by conventional tests and normalsperm-zona binding.Few of their sperm underwent the acrosome reaction on the surface of the zona and none penetrat-ed the zona.In contrast,fertilization and pregnancy rates were high with intmcytoplasmic sperm injection.We call thiscondition defective zona pellucida induced acrosome reaction.Discovery of the nature of the abnormalities in the signaltmnsduction and effector pathways of the human zona pellucida induced acrosome reaction should result in simpler testsand treatments for the patients and also provide new leads for contraceptive development.展开更多
文摘<abstract>Aim: We describe an approach to search for candidate genes for male infertility using the two human genome databases: the public University of California at Santa Cruz (UCSC) and private Celera databases which list known and predicted gene sequences and provide related information such as gene function, tissue expression, known mutations and single nucleotide polymorphisms (SNPs). Methods and Results: To demonstrate this in silico research, the following male infertility candidate genes were selected: (1) human BOULE, mutations of which may lead to germ cell arrest at the primary spermatocyte stage, (2) mutations of casein kinase 2 alpha genes which may cause globozoospermia, (3) DMR-N9 which is possibly involved in the spermatogenic defect of myotonic dystrophy and (4) several testes expressed genes at or near the breakpoints of a balanced translocation associated with hypospermatogenesis. We indicate how information derived from the human genome databases can be used to confirm these candidate genes may be pathogenic by studying RNA expression in tissue arrays using in situ hybridization and gene sequencing. Conclusion: The paper explains the new approach to discovering genetic causes of male infertility using information about the human genome.
文摘We developed tests of sperm-oocyte interaction:sperm-zona binding,zona-induced acrosome reaction,sperm-zona penetration and sperm-oolemma binding,using oocytes which failed to fertilise in clinical in vitro fertilization(IVF).Although oocyte defects contribute to failure of sperm oocyte interaction,rarely are all oocytes from one wom-an affected.Low or zero fertilization in standard IVFwas usually caused by sperm abnormalities.Poor sperm-zona pel-lucida binding was frequently associated with failure of standard IVF and obvious defects of sperm motility or morpholo-gy.The size and shape of the acrosome is particularly important for sperm binding to the oocyte.The proportion ofacrosome intact sperm in the insemination medium was related to the IVF rote.Inducing the acrosome reaction with acalcium ionophore reduced sperm-zona binding.Blocking acrosome dispersal with an acrosin inhibitor prevented sperm-zona penetration.Sperm-zona penetration was even more highly related to IVF rates than was sperm-zona binding.Some patients had low or zero fertilization rates with standard IVF but normal sperm by conventional tests and normalsperm-zona binding.Few of their sperm underwent the acrosome reaction on the surface of the zona and none penetrat-ed the zona.In contrast,fertilization and pregnancy rates were high with intmcytoplasmic sperm injection.We call thiscondition defective zona pellucida induced acrosome reaction.Discovery of the nature of the abnormalities in the signaltmnsduction and effector pathways of the human zona pellucida induced acrosome reaction should result in simpler testsand treatments for the patients and also provide new leads for contraceptive development.
