Effect of emotional stress on the frequency of meiotic abnormalities in male mice

The effect of stress on the recombination frequencies at the 1st and 2nd chromosomes of male mice was shown earlier. The purpose of this work is the study of the stress effects on the behaviour of meiotic chromosomes. Male mice (A/He and DD/J inbred strains) were treated with acute immobilizing stress at different periods, prior to killing. It was shown that the stress significantly increases the frequency of X-Y and autosomal univalents in metaphase 1 and aneuploidy in metaphase 2. The most sensitive to the stress are the late interphase - early leptotene cells.     

Effect of the mouse scid mutation on meiotic recombination

The goal of this study was to determine the effect of the mouse severe combined immunodeficiency (scid) mutation on the rate of meiotic recombination, by standard backcross linkage analysis. For this purpose, we examined four crosses that involved F₁ hybrid animals heterozygous for the strain C57BL/6 and BALB/c genomes. In one set of reciprocal crosses, F₁ animals were homozygous scid/scid, and in a second set of reciprocal crosses, F₁ mice were homozygous wild-type (+/+) at the scid locus. Backcross progeny were typed for recombination between selected genetic markers on mouse Chromosomes (Chrs) 1, 4, 6, 7, 9, 15, and 17. Although some differences in recombination were observed over some intervals, the expression of the SCID phenotype did not appear to have a major or consistent effect on meiotic recombination. Received: 4 October 1995 / Accepted: 2 April 1996     

Unlike other chemicals, etoposide (a topoisomerase-II inhibitor) produces peak mutagenicity in primary spermatocytes of the mouse

The cancer chemotherapy agent, and topoisomerase-II inhibitor, etoposide (VP-16) produced both recessive mutations at specific loci and dominants at other loci with peak frequencies in primary spermatocytes, a cell type in which the topo-II gene has been shown to be activated. Etoposide thus differs from all other chemicals whose germ-cell-stage specificity has been analyzed. No effects of etoposide exposure of spermatogonial stem cells ( 15,000 offspring scored) were detectable by either mutagenicity or productivity endpoints. The significant mutagenic response that followed exposure of poststem-cell stages ( 25,000 offspring scored) showed a clear peak, with three of four specific-locus mutants, and three of four dominant mutants conceived during weeks 4 or 5 (days 22–35) post-injection, a period that also encompassed the dominant-lethal peak. For this period, the induced specific-locus rate (with 95% confidence limits) at a weighted-average exposure of 75.1 mg etop/kg was 59.5 (14.6, 170.9) × 10⁻⁶/locus. At least 3 of the 4 specific-locus mutations were deletions, paralleling findings with etoposide or analogs in other test systems where a recombinational origin of the deletions has been suggested. Because, unlike other chemicals that induce deletions in male germ cells, etoposide is effective in stages normally associated with recombinational events, it will be of interest to determine whether this chemical can affect meiotic recombination.     

Effect of meiotic recombination on the production of aneuploid gametes in humans

Within the last decade, aberrant meiotic recombination has been confirmed as a molecular risk factor for chromosome nondisjunction in humans. Recombination tethers homologous chromosomes, linking and guiding them through proper segregation at meiosis I. In model organisms, mutations that disturb the recombination pathway increase the frequency of chromosome malsegregation and alterations in both the amount and placement of meiotic recombination are associated with nondisjunction. This association has been established for humans as well. Significant alterations in recombination have been found for all meiosis I-derived trisomies studied to date and a subset of so called "meiosis II" trisomy. Often exchange levels are reduced in a subset of cases where the nondisjoining chromosome fails to undergo recombination. For other trisomies, the placement of meiotic recombination has been altered. It appears that recombination too near the centromere or too far from the centromere imparts an increased risk for nondisjunction. Recent evidence from trisomy 21 also suggests an association may exist between recombination and maternal age, the most widely identified risk factor for aneuploidy. Among cases of maternal meiosis I-derived trisomy 21, increasing maternal age is associated with a decreasing frequency of recombination in the susceptible pericentromeric and telomeric regions. It is likely that multiple risk factors lead to nondisjunction, some age dependent and others age independent, some that act globally and others that are chromosome specific. Future studies are expected to shed new light on the timing and placement of recombination, providing additional clues to the link between altered recombination and chromosome nondisjunction.     

Synapsis and meiotic recombination in male Chinese muntjac (Muntiacus reevesi)

The muntjacs (Muntiacus, Cervidae) have been extensively studied in terms of chromosomal and karyotypic evolution. However, little is known about their meiotic chromosomes particularly the recombination patterns of homologous chromosomes. We used immunostained surface spreads to visualise synaptonemal complexes (SCs), recombination foci and kinetochores with antibodies against marker proteins. As in other mammals pachytene was the longest stage of meiotic prophase. 39.4% of XY bivalents lacked MLH1 foci compared to less than 0.5% of autosomes. The average number of MLH1 foci per pachytene cell in M. reevesi was 29.8. The distribution of MLH1 foci differed from other mammals. On SCs with one focus, the distribution was more even in M. reevesi than in other mammals; for SCs that have two or more MLH1 foci, usually there was a larger peak in the sub-centromere region than other regions on SC in M. reevesi. Additionally, there was a lower level of interference between foci in M. reevesi than in mouse or human. These observations may suggest that the regulation of homologous recombination in M. reevesi is slightly different from other mammals and will improve our understanding of the regulation of meiotic recombination, with respect to recombination frequency and position.     

Trans-centromere effects on meiotic recombination in the zebrafish

We report that lack of crossover along one chromosome arm is associated with high-frequency occurrence of recombination close to the opposing arm's centromere during zebrafish meiotic recombination. Our data indicate that recombination behavior on the two arms of a chromosome is linked. These results inform mapping strategies for telomeric mutants.     

RBFOX2缺失抑制雄性小鼠的减数分裂起始

减数分裂起始是配子发生的关键步骤。目前人们已经发现了一些减数分裂起始所必需的基因,但是对于该过程的调控基因及其作用机制还知之甚少。本实验室先前建立了精原干细胞（spermatogonial stem cells,SSCs）体外培养以及体外诱导减数分裂起始的技术体系,为更好地探究减数分裂起始调控基因及作用机理提供了良好的条件。实验室前期研究发现RNA结合蛋白RBFOX2可能调控减数分裂起始,然而RBFOX2在生殖细胞的减数分裂起始过程中的功能及作用机制还需深入研究。本研究利用慢病毒介导的转基因技术产生了RBFOX2敲降的精原干细胞系;发现RBFOX2敲降后,精原干细胞的自我更新、增殖以及分化未发生显著变化,但是减数分裂无法启动,分化型精原细胞发生明显凋亡。这一结果进一步显示了RNA结合蛋白在雄性动物减数分裂起始中的重要功能。     

The effects of ageing on the meiotic chromosomes of male and female mice

The effects of age on the chiasma frequencies, chiasma position and numbers of univalents at MI in males and females of three strains of mouse were examined. Males showed a slight but non significant rise in chiasma frequency in age due to an increase in bivalents with two chiasmata at the expense of single chiasmata bivalents. In contrast, females exhibited a significant decrease in chiasma frequency with age due to the loss of two chiasma bivalents with a corresponding increase in single terminal chiasmata bivalents. In both males and females there was no significant increase in univalents with age in the strains studied. Of interest was the finding of a greater degree of contraction of the MI chromosomes in the oocytes of old relative to young females, a differential contraction that was independent of culture time. This finding is discussed with regard to the production line theory and non disjunction at Anaphase in other strains of mice.     

Male-mediated effects on female meiotic recombination

Recombination rates vary owing to an individual's genetic composition and/or its environmental condition. Yet, the effects of mating partner on recombination rates have not been considered. Here, I document a previously undescribed, male-mediated effect on female recombination rates. After crossing females to males from different genetic backgrounds, I observed a significant difference in proportion of recombinant offspring based on the genetic background of the father (P= 0.0292; df = 3; F= 3.07). Genetic variation in male ability to affect recombination rate in their mates suggests the potential for sexual conflict on optimal proportion of recombinant offspring, perhaps leading to changes in population-level recombination rates with varying levels of sexual selection.     

Multiple mechanisms of meiotic recombination

In this issue, reveal that different meiotic recombination mechanisms predominate in fission yeast and budding yeast. Budding yeast usually form crossover recombinants through double Holliday junctions, whereas fission yeast unexpectedly appear to form crossover recombinants through single junctions.     

Targeted stimulation of meiotic recombination

Meiotic recombination in Saccharomyces cerevisiae is initiated by programmed DNA double-strand breaks (DSBs), a process that requires the Spo11 protein. DSBs usually occur in intergenic regions that display open chromatin accessibility, but other determinants that control their frequencies and non-random chromosomal distribution remain obscure. We report that a Spo11 construct bearing the Gal4 DNA binding domain not only rescues spo11Delta spore inviability and catalyzes DSB formation at natural sites but also strongly stimulates DSB formation near Gal4 binding sites. At GAL2, a naturally DSB-cold locus, Gal4BD-Spo11 creates a recombinational hotspot that depends on all the other DSB gene functions, showing that the targeting of Spo11 to a specific site is sufficient to stimulate meiotic recombination that is under normal physiological control.     

Managing meiotic recombination in plant breeding

Crossover recombination is a crucial process in plant breeding because it allows plant breeders to create novel allele combnations on chromosomes that can be used for breeding superior F1 hybrids. Gaining control over this process, in terms of increasing crossover incidence, altering crossover positions on chromosomes or silencing crossover formation, is essential for plant breeders to effectively engineer the allelic composition of chromosomes. We review the various means of crossover control that have been described or proposed. By doing so, we sketch a field of science that uses both knowledge from classic literature and the newest discoveries to manage the occurrence of crossovers for a variety of breeding purposes.     

Engineering meiotic recombination pathways in rice

In the last 15 years, outstanding progress has been made in understanding the function of meiotic genes in the model dicot and monocot plants Arabidopsis and rice (Oryza sativa L.), respectively. This knowledge allowed to modulate meiotic recombination in Arabidopsis and, more recently, in rice. For instance, the overall frequency of crossovers (COs) has been stimulated 2.3‐ and 3.2‐fold through the inactivation of the rice FANCM and RECQ4 DNA helicases, respectively, two genes involved in the repair of DNA double‐strand breaks (DSBs) as noncrossovers (NCOs) of the Class II crossover pathway. Differently, the programmed induction of DSBs and COs at desired sites is currently explored by guiding the SPO11‐1 topoisomerase‐like transesterase, initiating meiotic recombination in all eukaryotes, to specific target regions of the rice genome. Furthermore, the inactivation of 3 meiosis‐specific genes, namely PAIR1, OsREC8 and OsOSD1, in the Mitosis instead of Meiosis (MiMe) mutant turned rice meiosis into mitosis, thereby abolishing recombination and achieving the first component of apomixis, apomeiosis. The successful translation of Arabidopsis results into a crop further allowed the implementation of two breakthrough strategies that triggered parthenogenesis from the MiMe unreduced clonal egg cell and completed the second component of diplosporous apomixis. Here, we review the most recent advances in and future prospects of the manipulation of meiotic recombination in rice and potentially other major crops, all essential for global food security.     

Polymorphic variation in human meiotic recombination

In this study, our phenotype of interest is meiotic recombination. Using genotypes of approximately 6,000 SNP markers in members of the Centre d'Etude du Polymorphisme Humain Utah pedigrees, we found extensive individual variation in the number of female and male recombination events. The locations and frequencies of these recombination events vary along the genome. In both female and male meiosis, the regions with the most recombination events are found at the ends of the chromosomes. Our analysis also shows that there are polymorphic differences among individuals in the activity of the recombination "jungles"; these preferred sites of meiotic recombination differ greatly among individuals. These findings have important implications for understanding genetic disorders that result from improper chromosome segregation.     

CENP-B is not critical for meiotic chromosome segregation in male mice

Centromere protein B (CENP-B) is a constitutive protein that binds to a highly conserved 17 bp motif located at most mammalian centromeres. To determine whether disruption of this gene affects chromosome segregation in male germ cells, we evaluated the frequencies of disomic and diploid sperm in CENP-B heterozygous and homozygous null mice using the mouse epididymal sperm aneuploidy (m-ESA) assay, a multicolor FISH method with probes for chromosomes X, Y and 8. The specificity and sensitivity of the m-ESA assay was demonstrated using Robertsonian (2.8) translocation heterozygotes as positive controls for sperm aneuploidy. Our results show that the frequencies of disomic and diploid sperm did not differ significantly between CENP-B heterozygous and homozygous null mice (P≥0.5) or from 129/Swiss isogenic mice (P≥0.5) and B6C3F1 mice (P≥0.2). These findings indicate that CENP-B does not have an essential role during chromosome segregation in male meiosis.     

Role of ubiquitination in meiotic recombination repair

Programmed and unprogrammed double-strand breaks (DSBs) often arise from such physiological requirements as meiotic recombination, and exogenous insults, such as ionizing radiation (IR). Due to deleterious impacts on genome stability, DSBs must be appropriately processed and repaired in a regulatory manner. Recent investigations have indicated that ubiquitination is a critical factor in DNA damage response and meiotic recombination repair. This review summarizes the effects of proteins and complexes associa...     

Epigenetic control of meiotic recombination in plants

Meiotic recombination is a deeply conserved process within eukaryotes that has a profound effect on patterns of natural genetic variation. During meiosis homologous chromosomes pair and undergo DNA double strand breaks generated by the Spo11 endonuclease. These breaks can be repaired as crossovers that result in reciprocal exchange between chromosomes. The frequency of recombination along chromosomes is highly variable, for example, crossovers are rarely observed in heterochromatin and the centromeric regions. Recent work in plants has shown that crossover hotspots occur in gene promoters and are associated with specific chromatin modifications, including H2 A.Z. Meiotic chromosomes are also organized in loop-base arrays connected to an underlying chromosome axis, which likely interacts with chromatin to organize patterns of recombination.Therefore, epigenetic information exerts a major influence on patterns of meiotic recombination along chromosomes, genetic variation within populations and evolution of plant genomes.