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Open AccessOpen Access JUSTC Original Paper

Alteration in meiotic recombination in human male infertility

  • Hefei National Laboratory for Physical Sciences at Microscale, and School of Life Sciences, University of Science and Technology of China, Hefei 230027, China

Cite this:
  • Received Date: 28 June 2008
  • Rev Recd Date: 05 July 2008
  • Publish Date: 31 August 2008
    Abstract

  • Abstract

    During the prophase of meiosis I, homologous chromosomes pair, synapse and exchange genetic materials (recombination). Meiotic recombination plays a crucial role in the proper segregation of homologous chromosomes and normal gametogenesis. Altered recombination may lead to various sperm abnormalities, such as arrest in spermatogenesis or non-disjunction, which in turn contributes to infertility or aneuploidy. Infertility is a major health problem that affects 10%~15% of couples, about half of which being attributed to male factors in which the aetiology and mechanisms are unidentified. Despite the obvious clinical significance and high incidence of human male infertility, the mechanisms of spermatogenic failure caused by meiotic recombination errors in humans has been inadequately unclear. However, recently-developed immunofluorescence methods which can directly view meiotic recombination and associated important events during gametogenesis have revolutionized our understanding of human spermatogenesis. In this paper, the relationship between meiotic recombination and spermatogenesis is reviewed.

    Abstract

    During the prophase of meiosis I, homologous chromosomes pair, synapse and exchange genetic materials (recombination). Meiotic recombination plays a crucial role in the proper segregation of homologous chromosomes and normal gametogenesis. Altered recombination may lead to various sperm abnormalities, such as arrest in spermatogenesis or non-disjunction, which in turn contributes to infertility or aneuploidy. Infertility is a major health problem that affects 10%~15% of couples, about half of which being attributed to male factors in which the aetiology and mechanisms are unidentified. Despite the obvious clinical significance and high incidence of human male infertility, the mechanisms of spermatogenic failure caused by meiotic recombination errors in humans has been inadequately unclear. However, recently-developed immunofluorescence methods which can directly view meiotic recombination and associated important events during gametogenesis have revolutionized our understanding of human spermatogenesis. In this paper, the relationship between meiotic recombination and spermatogenesis is reviewed.
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    • References(50)
  • [1]
    Tsujimura A, Matsumiya K, Miyagawa Y, et al. Prediction of successful outcome of microdissection testicular sperm extraction in men with idiopathic nonobstructive azoospermia[J]. J Urol, 2004, 172: 1 944-1 947.
    [2]
    Hassold T, Hunt P. To err (meiotically) is human: The genesis of human aneuploidy[J]. Nature Review Genetics,2001, 2: 280-291.
    [3]
    Lange R, Krause W, Engel W. Analyses of meiotic chromosomes in testicular biopsies of infertile patients[J]. Human Reproduction,1997, 12: 2 154-2 158.
    [4]
    Vendrell J M, Garcia F, Veiga A, et al. Meiotic abnormalities and spermatogenic parameters in severe oligoasthenozoospermia[J]. Hum Reprod,1999, 14: 375-378.
    [5]
    Guichaoua M R, Perrin J, Metzler-Guillemain C, et al. Meiotic anomalies in infertile men with severe spermatogenic defects[J]. Human Reproduction, 2005, 20: 1 897-1 902.
    [6]
    Sun F, Oliver-Bonet M, Liehr T, et al. Human male recombination maps for individual chromosomes[J]. Am J Hum Genet,2004, 74: 521-531.
    [7]
    Hassold T, Sherman S, Hunt P. Counting cross-overs: characterizing meiotic recombination in mammals[J]. Hum Mol Genet,2000, 9: 2 409-2 419.
    [8]
    White E J, Cowan C, Cande W Z, et al. In vivo analysis of synaptonemal complex formation during yeast meiosis[J]. Genetics,2004, 167: 51-63.
    [9]
    Bishop D K, Zickler D. Early decision; meiotic crossover interference prior to stable strand exchange and synapsis[J]. Cell,2004, 117: 9-15.
    [10]
    Chua P R, Roeder G S. Tam1, a telomere-associated meiotic protein, functions in chromosome synapsis and crossover interference[J]. Genes Dev,1997, 11: 1 786-1 800.
    [11]
    Gorlov I P, Zhelezova A I, Gorlova O. Sex differences in chiasma distribution along two marked mouse chromosomes: differences in chiasma distribution as a reason for sex differences in recombination frequency[J]. Genetical research,1994, 64: 161-166.
    [12]
    Lawrie N M, Tease C, Hultén M A. Chiasma frequency, distribution and interference maps of mouse autosomes[J]. Chromosoma,1995, 104: 308-314.
    [13]
    True J R, Mercer J M, Laurie C C. Differences in crossover frequency and distribution among three sibling species of Drosophila[J]. Genetics,1996, 142: 507-523.
    [14]
    Sun F, Trpkov K, Rademaker A, et al. Variation in meiotic recombination frequencies among human males[J]. Hum Genet,2005, 116: 172-178.
    [15]
    Sun F, Oliver-Bonet M, Liehr T, et al. Variation in MLH1 distribution in recombination maps for individual chromosomes from human males[J]. Hum Mol Genet,2006, 15: 2 376-2 391.
    [16]
    Koehler K E, Cherry J P, Lynn A, et al. Genetic control of mammalian meiotic recombination. I. Variation in exchange frequencies among males from inbred mouse strains[J]. Genetics,2002, 162: 297-306.
    [17]
    Tanzi R E, Watkins P C, Stewart G D, et al. A genetic linkage map of human chromosome 21: analysis of recombination as a function of sex and age[J]. American Journal Human Genetics,1992, 50: 551-558.
    [18]
    Rose A, Baillie D. The effect of temperature and parental age on recombination and nondisjunction in C. elegans[J]. Genetics,1979, 92: 409-418.
    [19]
    Sun F, Kozak G, Scott S, et al. Meiotic defects in a man with non-obstructive azoospermia: case report[J]. Hum Reprod,2004, 19: 1 770-1 773.
    [20]
    Sun F, Oliver-Bonet M, Liehr T, et al. Discontinuities and unsynapsed regions in meiotic chromosomes have a cis effect on meiotic recombination patterns in normal human males[J]. Hum Mol Genet,2005, 14: 3 013-3 018.
    [21]
    Luthardt F W, Palmer C G, Yu P. Chiasma and univalent frequencies in aging female mice[J]. Cytogenetics and Cell Genetics,1973, 12: 68-79.
    [22]
    Jagiello G, Fang J S. Analyses of diplotene chiasma frequencies in mouse oocytes and spermatocytes in relation to ageing and sexual dimorphism[J]. Cytogenetics and Cell Genetics,1979, 23: 53-60.
    [23]
    Sugawara S, Mikamo K. Absence of correlation between univalent formation and meiotic nondisjunction in aged female Chinese hamsters[J]. Cytogenetics and Cell Genetics,1983, 35: 34-40.
    [24]
    Broman K, Murray J, Sheffield V, et al. Comprehensive human genetic maps: individual and sex-specific variation in recombination[J]. American Journal of Human Genetics,1998, 63: 861-869.
    [25]
    Lynn A, Koehler K E, Judis L, et al. Covariation of synaptonemal complex length and mammalian meiotic exchange rates[J]. Science,2002, 296: 2 222-2 225.
    [26]
    Egozcue J, Templado C, Vidal F, et al. Meiotic studies in a series of 1100 infertile and sterile males[J]. Hum Genet,1983, 65: 185-188.
    [27]
    Bascom-Slack C, Ross L, Dawson D. Chiasmata, crossovers, and meiotic chromosome segregation[J]. Advances in Human Genetics,1997, 35: 253-283.
    [28]
    Roeder G S, Bailis J M. The pachytene checkpoint[J]. Trends in Genetics,2000, 16: 395-403.
    [29]
    Sun F, Oliver-Bonet M, Liehr T, et al. Analysis of non-crossover bivalents in pachytene cells from 10 normal men[J]. Hum Reprod,2006, 21: 2 335-2 339.
    [30]
    Sun F, Mikhaail-Philips M, Oliver-Bonet M, et al. The relationship between meiotic recombination in human spermatocytes and aneuploidy in sperm[J]. Hum Reprod,2008(in press).
    [31]
    Sun F, Oliver-Bonet M, Liehr T, et al. Discontinuities and unsynapsed regions in meiotic chromosomes have a trans effect on meiotic recombination of some chromosomes in human males[J]. Cytogenet Genome Res,2007, 119: 27-32.
    [32]
    Hassold T, Merrill M, Adkins K, et al. Recombination and maternal age-dependent nondisjunction: molecular studies of trisomy 16[J]. Am J Hum Genet,1995, 57: 867-874.
    [33]
    Lamb N E, Feingold E, Savage A, et al. Characterization of susceptible chiasma configurations that increase the risk for maternal nondisjunction of chromosome 21[J]. Hum Mol Genet,1997, 6: 1 391-1 399.
    [34]
    Bugge M, Collins A, Petersen M B, et al. Non-disjunction of chromosome 18[J]. Hum Mol Genet,1998, 7: 661-669.
    [35]
    Roeder G S. Meiotic chromosomes: it takes two to tango[J]. Genes Development,1997, 11: 2 600-2 621.
    [36]
    Ross L O, Maxfield R, Dawson D. Exchanges are not equally able to enhance meiotic chromosome segregation in yeast[J]. Procedings of the National Academic of Science of the United States of America,1996, 93: 4 979-4 983.
    [37]
    Krawchuk M D, Wahls W P. Centromere mapping functions for aneuploid meiotic products: Analysis of rec8, rec10 and rec11 mutants of the fission yeast Schizosaccharomyces pombe[J]. Genetics,1999, 153: 49-55.
    [38]
    Gonsalves J, Sun F, Schlegal P, et al. Defective recombination in infertile men[J]. Human Molecular Genetics,2004, 13: 2 875-2 883.
    [39]
    Sun F, Greene C, Turek P J, et al. Immunofluorescent synaptonemal complex analysis in azoospermic men[J]. Cytogenetic and Genome Research,2005, 111: 366-370.
    [40]
    Sun F, Kozak G, Scott S, et al. Meiotic defects in a man with non-obstructive azoospermia: Case report[J]. Human Reproduction,2004, 19: 1 770-1 773.
    [41]
    Sun F, Turek P, Greene C, et al. Abnormal progression through meiosis in men with nonobstructive azoospermia[J]. Fertil Steril,2007, 87: 565-571.
    [42]
    Judis L, Chan E R, Schwartz S, et al. Meiosis I arrest and azoospermia in an infertile male explained by failure of formation of a component of the synaptonemal complex[J]. Fertil Steril,2004, 81: 205-209.
    [43]
    Topping D, Brown P, Judis L, et al. Synaptic defects at meiosis I and non-obstructive azoospermia[J]. Hum Reprod,2006, 21: 3 171-3 177.
    [44]
    Sun F, Oliver-Bonet M, Turek P J, et al. Meiotic studies in an azoospermic human translocation (Y;1) carrier[J]. Mol Hum Reprod,2005, 11: 361-364.
    [45]
    Oliver-Bonet M, Benet J, Sun F, et al. Meiotic studies in two human reciprocal translocations and their association with spermatogenic failure[J]. Hum Reprod,2005, 20: 683-688.
    [46]
    Yuan L, Liu J G, Zhao J, et al. The murine SCP3 gene is required for synaptonemal complex assembly, chromosome synapsis, and male fertility[J]. Mol Cell,2000, 5: 73-83.
    [47]
    Yang F, De La Fuente R, Leu N A, et al. Mouse SYCP2 is required for synaptonemal complex assembly and chromosomal synapsis during male meiosis[J]. J Cell Biol,2006, 173: 497-507.
    [48]
    Sharan S K, Pyle A, Coppola V, et al. BRCA2 deficiency in mice leads to meiotic impairment and infertility[J]. Development,2004, 131: 131-142.
    [49]
    Kneitz B, Cohen P E, Avdievich E, et al. MutS homolog 4 localization to meiotic chromosomes is required for chromosome pairing during meiosis in male and female mice[J]. Genes and Development,2000, 14: 1 085-1 097.
    [50]
    Webster K E, OBryan M K, Fletcher S, et al. Meiotic and epigenetic defects in Dnmt3L-knockout mouse spermatogenesis[J]. Proc Natl Acad Sci U S A,2005, 102: 4 068-4 073.
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    [1]
    Tsujimura A, Matsumiya K, Miyagawa Y, et al. Prediction of successful outcome of microdissection testicular sperm extraction in men with idiopathic nonobstructive azoospermia[J]. J Urol, 2004, 172: 1 944-1 947.
    [2]
    Hassold T, Hunt P. To err (meiotically) is human: The genesis of human aneuploidy[J]. Nature Review Genetics,2001, 2: 280-291.
    [3]
    Lange R, Krause W, Engel W. Analyses of meiotic chromosomes in testicular biopsies of infertile patients[J]. Human Reproduction,1997, 12: 2 154-2 158.
    [4]
    Vendrell J M, Garcia F, Veiga A, et al. Meiotic abnormalities and spermatogenic parameters in severe oligoasthenozoospermia[J]. Hum Reprod,1999, 14: 375-378.
    [5]
    Guichaoua M R, Perrin J, Metzler-Guillemain C, et al. Meiotic anomalies in infertile men with severe spermatogenic defects[J]. Human Reproduction, 2005, 20: 1 897-1 902.
    [6]
    Sun F, Oliver-Bonet M, Liehr T, et al. Human male recombination maps for individual chromosomes[J]. Am J Hum Genet,2004, 74: 521-531.
    [7]
    Hassold T, Sherman S, Hunt P. Counting cross-overs: characterizing meiotic recombination in mammals[J]. Hum Mol Genet,2000, 9: 2 409-2 419.
    [8]
    White E J, Cowan C, Cande W Z, et al. In vivo analysis of synaptonemal complex formation during yeast meiosis[J]. Genetics,2004, 167: 51-63.
    [9]
    Bishop D K, Zickler D. Early decision; meiotic crossover interference prior to stable strand exchange and synapsis[J]. Cell,2004, 117: 9-15.
    [10]
    Chua P R, Roeder G S. Tam1, a telomere-associated meiotic protein, functions in chromosome synapsis and crossover interference[J]. Genes Dev,1997, 11: 1 786-1 800.
    [11]
    Gorlov I P, Zhelezova A I, Gorlova O. Sex differences in chiasma distribution along two marked mouse chromosomes: differences in chiasma distribution as a reason for sex differences in recombination frequency[J]. Genetical research,1994, 64: 161-166.
    [12]
    Lawrie N M, Tease C, Hultén M A. Chiasma frequency, distribution and interference maps of mouse autosomes[J]. Chromosoma,1995, 104: 308-314.
    [13]
    True J R, Mercer J M, Laurie C C. Differences in crossover frequency and distribution among three sibling species of Drosophila[J]. Genetics,1996, 142: 507-523.
    [14]
    Sun F, Trpkov K, Rademaker A, et al. Variation in meiotic recombination frequencies among human males[J]. Hum Genet,2005, 116: 172-178.
    [15]
    Sun F, Oliver-Bonet M, Liehr T, et al. Variation in MLH1 distribution in recombination maps for individual chromosomes from human males[J]. Hum Mol Genet,2006, 15: 2 376-2 391.
    [16]
    Koehler K E, Cherry J P, Lynn A, et al. Genetic control of mammalian meiotic recombination. I. Variation in exchange frequencies among males from inbred mouse strains[J]. Genetics,2002, 162: 297-306.
    [17]
    Tanzi R E, Watkins P C, Stewart G D, et al. A genetic linkage map of human chromosome 21: analysis of recombination as a function of sex and age[J]. American Journal Human Genetics,1992, 50: 551-558.
    [18]
    Rose A, Baillie D. The effect of temperature and parental age on recombination and nondisjunction in C. elegans[J]. Genetics,1979, 92: 409-418.
    [19]
    Sun F, Kozak G, Scott S, et al. Meiotic defects in a man with non-obstructive azoospermia: case report[J]. Hum Reprod,2004, 19: 1 770-1 773.
    [20]
    Sun F, Oliver-Bonet M, Liehr T, et al. Discontinuities and unsynapsed regions in meiotic chromosomes have a cis effect on meiotic recombination patterns in normal human males[J]. Hum Mol Genet,2005, 14: 3 013-3 018.
    [21]
    Luthardt F W, Palmer C G, Yu P. Chiasma and univalent frequencies in aging female mice[J]. Cytogenetics and Cell Genetics,1973, 12: 68-79.
    [22]
    Jagiello G, Fang J S. Analyses of diplotene chiasma frequencies in mouse oocytes and spermatocytes in relation to ageing and sexual dimorphism[J]. Cytogenetics and Cell Genetics,1979, 23: 53-60.
    [23]
    Sugawara S, Mikamo K. Absence of correlation between univalent formation and meiotic nondisjunction in aged female Chinese hamsters[J]. Cytogenetics and Cell Genetics,1983, 35: 34-40.
    [24]
    Broman K, Murray J, Sheffield V, et al. Comprehensive human genetic maps: individual and sex-specific variation in recombination[J]. American Journal of Human Genetics,1998, 63: 861-869.
    [25]
    Lynn A, Koehler K E, Judis L, et al. Covariation of synaptonemal complex length and mammalian meiotic exchange rates[J]. Science,2002, 296: 2 222-2 225.
    [26]
    Egozcue J, Templado C, Vidal F, et al. Meiotic studies in a series of 1100 infertile and sterile males[J]. Hum Genet,1983, 65: 185-188.
    [27]
    Bascom-Slack C, Ross L, Dawson D. Chiasmata, crossovers, and meiotic chromosome segregation[J]. Advances in Human Genetics,1997, 35: 253-283.
    [28]
    Roeder G S, Bailis J M. The pachytene checkpoint[J]. Trends in Genetics,2000, 16: 395-403.
    [29]
    Sun F, Oliver-Bonet M, Liehr T, et al. Analysis of non-crossover bivalents in pachytene cells from 10 normal men[J]. Hum Reprod,2006, 21: 2 335-2 339.
    [30]
    Sun F, Mikhaail-Philips M, Oliver-Bonet M, et al. The relationship between meiotic recombination in human spermatocytes and aneuploidy in sperm[J]. Hum Reprod,2008(in press).
    [31]
    Sun F, Oliver-Bonet M, Liehr T, et al. Discontinuities and unsynapsed regions in meiotic chromosomes have a trans effect on meiotic recombination of some chromosomes in human males[J]. Cytogenet Genome Res,2007, 119: 27-32.
    [32]
    Hassold T, Merrill M, Adkins K, et al. Recombination and maternal age-dependent nondisjunction: molecular studies of trisomy 16[J]. Am J Hum Genet,1995, 57: 867-874.
    [33]
    Lamb N E, Feingold E, Savage A, et al. Characterization of susceptible chiasma configurations that increase the risk for maternal nondisjunction of chromosome 21[J]. Hum Mol Genet,1997, 6: 1 391-1 399.
    [34]
    Bugge M, Collins A, Petersen M B, et al. Non-disjunction of chromosome 18[J]. Hum Mol Genet,1998, 7: 661-669.
    [35]
    Roeder G S. Meiotic chromosomes: it takes two to tango[J]. Genes Development,1997, 11: 2 600-2 621.
    [36]
    Ross L O, Maxfield R, Dawson D. Exchanges are not equally able to enhance meiotic chromosome segregation in yeast[J]. Procedings of the National Academic of Science of the United States of America,1996, 93: 4 979-4 983.
    [37]
    Krawchuk M D, Wahls W P. Centromere mapping functions for aneuploid meiotic products: Analysis of rec8, rec10 and rec11 mutants of the fission yeast Schizosaccharomyces pombe[J]. Genetics,1999, 153: 49-55.
    [38]
    Gonsalves J, Sun F, Schlegal P, et al. Defective recombination in infertile men[J]. Human Molecular Genetics,2004, 13: 2 875-2 883.
    [39]
    Sun F, Greene C, Turek P J, et al. Immunofluorescent synaptonemal complex analysis in azoospermic men[J]. Cytogenetic and Genome Research,2005, 111: 366-370.
    [40]
    Sun F, Kozak G, Scott S, et al. Meiotic defects in a man with non-obstructive azoospermia: Case report[J]. Human Reproduction,2004, 19: 1 770-1 773.
    [41]
    Sun F, Turek P, Greene C, et al. Abnormal progression through meiosis in men with nonobstructive azoospermia[J]. Fertil Steril,2007, 87: 565-571.
    [42]
    Judis L, Chan E R, Schwartz S, et al. Meiosis I arrest and azoospermia in an infertile male explained by failure of formation of a component of the synaptonemal complex[J]. Fertil Steril,2004, 81: 205-209.
    [43]
    Topping D, Brown P, Judis L, et al. Synaptic defects at meiosis I and non-obstructive azoospermia[J]. Hum Reprod,2006, 21: 3 171-3 177.
    [44]
    Sun F, Oliver-Bonet M, Turek P J, et al. Meiotic studies in an azoospermic human translocation (Y;1) carrier[J]. Mol Hum Reprod,2005, 11: 361-364.
    [45]
    Oliver-Bonet M, Benet J, Sun F, et al. Meiotic studies in two human reciprocal translocations and their association with spermatogenic failure[J]. Hum Reprod,2005, 20: 683-688.
    [46]
    Yuan L, Liu J G, Zhao J, et al. The murine SCP3 gene is required for synaptonemal complex assembly, chromosome synapsis, and male fertility[J]. Mol Cell,2000, 5: 73-83.
    [47]
    Yang F, De La Fuente R, Leu N A, et al. Mouse SYCP2 is required for synaptonemal complex assembly and chromosomal synapsis during male meiosis[J]. J Cell Biol,2006, 173: 497-507.
    [48]
    Sharan S K, Pyle A, Coppola V, et al. BRCA2 deficiency in mice leads to meiotic impairment and infertility[J]. Development,2004, 131: 131-142.
    [49]
    Kneitz B, Cohen P E, Avdievich E, et al. MutS homolog 4 localization to meiotic chromosomes is required for chromosome pairing during meiosis in male and female mice[J]. Genes and Development,2000, 14: 1 085-1 097.
    [50]
    Webster K E, OBryan M K, Fletcher S, et al. Meiotic and epigenetic defects in Dnmt3L-knockout mouse spermatogenesis[J]. Proc Natl Acad Sci U S A,2005, 102: 4 068-4 073.
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