Sexual reproduction in diploid organisms requires the production of haploid gametes via the process of meiosis, in which a single round of DNA replication is followed by two consecutive cell divisions （or two nuclear...Sexual reproduction in diploid organisms requires the production of haploid gametes via the process of meiosis, in which a single round of DNA replication is followed by two consecutive cell divisions （or two nuclear divisions and one cytokinesis）. In the majority of known cases the proper segregation of the parental genome into gametes is accom- panied and facilitated by meiotic crossover formation, which contributes to physical association between homologous chromosomes and results in the generation of new combina- tions of alleles in the progeny. This is necessarily a complex and highly regulated process with multiple steps in a tight sequence, including exit from mitosis, DNA double strand break （DSB） formation, homology search, recombinational repair of DSBs and regulation of cohesion between homolo- gous chromosomes. The process of meiosis is astonishingly effective, even in mammals and flowering plants with extremely large genomes, in which this entails the manipula- tion of approximately twelve metres or even more of the replicated diploid DNA, on the order of 10^10 base pairs, with close to base pair accuracy. In plants, meiosis does not pro- duce gametes directly, but progenitors of haploid multicellular structures called gametophytes, which contain haploid cells that differentiate into gametes.展开更多
Meiosis is a key event in gametogenesis that generates new combinations of genetic information and is required to reduce the chro- mosome content of the gametes. Meiotic chromosomes undergo a number of specialised eve...Meiosis is a key event in gametogenesis that generates new combinations of genetic information and is required to reduce the chro- mosome content of the gametes. Meiotic chromosomes undergo a number of specialised events during prophase to allow meiotic recombination, homologous chromosome synapsis and reductional chromosome segregation to occur. In mammalian cells, DNA phys- ically associates with histones to form chromatin, which can be modified by methylation, phosphorylation, ubiquitination and acetylation to help regulate higher order chromatin structure, gene expression, and chromosome organisation. Recent studies have identified some of the enzymes responsible for generating chromatin modifications in meiotic mammalian cells, and shown that these chromatin modifying enzymes are required for key meiosis-specific events that occur during meiotic prophase. This review will discuss the role of chromatin modifications in meiotic recombination, homologous chromosome synapsis and regulation of meiotic gene expression in mammals.展开更多
β-defensin peptides are a large family of antimicrobial peptides. Although they kill microbes in vitroand interact with immune cells, the precise role of these genes in vivo remains uncertain. Despite their inducible...β-defensin peptides are a large family of antimicrobial peptides. Although they kill microbes in vitroand interact with immune cells, the precise role of these genes in vivo remains uncertain. Despite their inducible presence at mucosal surfaces, their main site of expression is the epididymis. Recent evidence suggests that a major function of these peptides is in sperm maturation. In addition to previous work suggesting this, work at the MRC Human Genetics Unit, Edinburgh, has shown that homozygous deletion of a cluster of nine β-defensin genes in the mouse results in profound male sterility. The spermatozoa derived from the mutants had reduced motility and increased fragility. Epididymal spermatozoa isolated from the cauda region of the homozygous mutants demonstrated precocious capacitation and increased spontaneous acrosome reactions compared with those from wild-types. Despite this, these mutant spermatozoa had reduced ability to bind to the zona pellucida of oocytes. Ultrastructural examination revealed a disintegration of the microtubule structure of mutant-derived spermatozoa isolated from the epididymal cauda region, but not from the caput. Consistent with premature acrosome reaction and hyperactivation, spermatozoa from mutant animals had significantly increased intracellular calcium content. This work demonstrates that in vivo β-defensins are essential for successful sperm maturation, and that their disruption alters intracellular calcium levels, which most likely leads to premature activation and spontaneous acrosome reactions that result in hyperactivation and loss of microtubule structure of the axoneme. Determining which of the nine genes are responsible for the phenotype and the relevance to human sperm function is important for future work on male infertility.展开更多
文摘Sexual reproduction in diploid organisms requires the production of haploid gametes via the process of meiosis, in which a single round of DNA replication is followed by two consecutive cell divisions （or two nuclear divisions and one cytokinesis）. In the majority of known cases the proper segregation of the parental genome into gametes is accom- panied and facilitated by meiotic crossover formation, which contributes to physical association between homologous chromosomes and results in the generation of new combina- tions of alleles in the progeny. This is necessarily a complex and highly regulated process with multiple steps in a tight sequence, including exit from mitosis, DNA double strand break （DSB） formation, homology search, recombinational repair of DSBs and regulation of cohesion between homolo- gous chromosomes. The process of meiosis is astonishingly effective, even in mammals and flowering plants with extremely large genomes, in which this entails the manipula- tion of approximately twelve metres or even more of the replicated diploid DNA, on the order of 10^10 base pairs, with close to base pair accuracy. In plants, meiosis does not pro- duce gametes directly, but progenitors of haploid multicellular structures called gametophytes, which contain haploid cells that differentiate into gametes.
基金supported by a Medical Research Council (MRC)intramural program grant to I.R.A.at the MRC Human Genetics Unit in UK
文摘Meiosis is a key event in gametogenesis that generates new combinations of genetic information and is required to reduce the chro- mosome content of the gametes. Meiotic chromosomes undergo a number of specialised events during prophase to allow meiotic recombination, homologous chromosome synapsis and reductional chromosome segregation to occur. In mammalian cells, DNA phys- ically associates with histones to form chromatin, which can be modified by methylation, phosphorylation, ubiquitination and acetylation to help regulate higher order chromatin structure, gene expression, and chromosome organisation. Recent studies have identified some of the enzymes responsible for generating chromatin modifications in meiotic mammalian cells, and shown that these chromatin modifying enzymes are required for key meiosis-specific events that occur during meiotic prophase. This review will discuss the role of chromatin modifications in meiotic recombination, homologous chromosome synapsis and regulation of meiotic gene expression in mammals.
文摘β-defensin peptides are a large family of antimicrobial peptides. Although they kill microbes in vitroand interact with immune cells, the precise role of these genes in vivo remains uncertain. Despite their inducible presence at mucosal surfaces, their main site of expression is the epididymis. Recent evidence suggests that a major function of these peptides is in sperm maturation. In addition to previous work suggesting this, work at the MRC Human Genetics Unit, Edinburgh, has shown that homozygous deletion of a cluster of nine β-defensin genes in the mouse results in profound male sterility. The spermatozoa derived from the mutants had reduced motility and increased fragility. Epididymal spermatozoa isolated from the cauda region of the homozygous mutants demonstrated precocious capacitation and increased spontaneous acrosome reactions compared with those from wild-types. Despite this, these mutant spermatozoa had reduced ability to bind to the zona pellucida of oocytes. Ultrastructural examination revealed a disintegration of the microtubule structure of mutant-derived spermatozoa isolated from the epididymal cauda region, but not from the caput. Consistent with premature acrosome reaction and hyperactivation, spermatozoa from mutant animals had significantly increased intracellular calcium content. This work demonstrates that in vivo β-defensins are essential for successful sperm maturation, and that their disruption alters intracellular calcium levels, which most likely leads to premature activation and spontaneous acrosome reactions that result in hyperactivation and loss of microtubule structure of the axoneme. Determining which of the nine genes are responsible for the phenotype and the relevance to human sperm function is important for future work on male infertility.
