Skip to main content
Log in

Mutant meiotic chromosome core components in mice can cause apparent sexual dimorphic endpoints at prophase or X–Y defective male-specific sterility

  • Research Article
  • Published:
Chromosoma Aims and scope Submit manuscript

Abstract

Genetic modifications causing germ cell death during meiotic prophase in the mouse frequently have sexually dimorphic phenotypes where oocytes reach more advanced stages than spermatocytes. To determine to what extent these dimorphisms are due to differences in male versus female meiotic prophase development, we compared meiotic chromosome events in the two sexes in both wild-type and mutant mice. We report the abundance and time course of appearance of structural and recombination-related proteins of fetal oocyte nuclei. Oocytes at successive days post coitus show rapid, synchronous meiotic prophase development compared with the continuous spermatocyte development in adult testis. Consequently, a genetic defect requiring 2–3 days from the onset of prophase to reach arrest registers pachytene as the developmental endpoint in oocytes. Pachytene spermatocytes, on the other hand, which normally accumulate during days 4–10 after the onset of prophase, will be rare, giving the appearance of an earlier endpoint than in oocytes. We conclude that these different logistics create apparent sexually dimorphic endpoints. For more pronounced sexual dimorphisms, we examined meiotic prophase of mice with genetic modifications of meiotic chromosome core components that cause male but not female sterility. The correlations between male sterility and alterations in the organization of the sex chromosome cores and X–Y chromatin may indicate that impaired signals from the XY domain (XY chromosome cores, chromatin, dense body and sex body) may interfere with the progression of the spermatocyte through prophase. Oocytes, in the absence of the X–Y pair, do not suffer such defects.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2a–d
Fig. 3
Fig. 4
Fig. 5a–h
Fig. 6a,b
Fig. 7a,b
Fig. 8a–g
Fig. 9

Similar content being viewed by others

References

  • Baudat F, Manova K, Yuen JP, Jasin M, Keeney S (2000) Chromosome synapsis defects and sexually dimorphic meiotic progression in mice lacking Spo11. Mol Cell 6:989–998

    Article  CAS  PubMed  Google Scholar 

  • Celeste A, Petersen S, Romanienko PJ, Fernandez-Capetillo O, Chen HT, Sedelnikova OA, Reina-San-Martin B, Coppola V, Meffre E, Difilippantonio MJ et al (2002) Genomic instability in mice lacking histone H2AX. Science 296:922–927

    Article  CAS  PubMed  Google Scholar 

  • Clermont Y, Trott M (1969) Duration of the cycle of the seminiferous epithelium in the mouse and hamster determined by means of 3H-thymidine and radioautography. Fertil Steril 20:805–817

    CAS  PubMed  Google Scholar 

  • Crackower MA, Kolas NK, Noguchi J, Sarao R, Kikuchi K, Kaneko H, Kobayashi E, Kawai Y, Kozieradzki I, Landers R et al (2003) Essential role of Fkbp6 in male fertility and homologous chromosome pairing in meiosis. Science 300:1291–1295

    Article  CAS  PubMed  Google Scholar 

  • Di Giacomo M, Barchi M, Baudat F, Edelmann W, Keeney S, Jasin M (2005) Distinct DNA-damage-dependent and -independent responses drive the loss of oocytes in recombination-defective mouse mutants. Proc Natl Acad Sci U S A 102:737–742

    Article  PubMed  Google Scholar 

  • Dobson MJ, Pearlman RE, Karaiskakis A, Spyropoulos B, Moens PB (1994) Synaptonemal complex proteins: occurrence, epitope mapping and chromosome disjunction. J Cell Sci 107:2749–2760

    CAS  PubMed  Google Scholar 

  • Dresser ME, Moses MJ (1980) Synaptonemal complex karyotyping in spermatocytes of the Chinese hamster (Cricetulus griseus): IV. Light and electron microscopy of synapsis and nucleolar development by silver staining. Chromosoma 76:1–22

    Article  CAS  PubMed  Google Scholar 

  • Edelmann W, Cohen PE, Kane M, Lau K, Morrow B, Bennett S, Umar A, Kunkel T, Cattoretti G, Chaganti R et al (1996) Meiotic pachytene arrest in MLH1-deficient mice. Cell 85:1125–1134

    Article  CAS  PubMed  Google Scholar 

  • Eijpe M, Heyting C, Gross B, Jessberger R (2000) Association of mammalian SMC1 and SMC3 proteins with meiotic chromosomes and synaptonemal complexes. J Cell Sci 113:673–682

    CAS  PubMed  Google Scholar 

  • Fernandez-Capetillo O, Mahadevaiah SK, Celeste A, Romanienko PJ, Camerini-Otero RD, Bonner WM, Manova K, Burgoyne P, Nussenzweig A (2003) H2AX is required for chromatin remodeling and inactivation of sex chromosomes in male mouse meiosis. Dev Cell 4:497–508

    Article  CAS  PubMed  Google Scholar 

  • Habu T, Taki T, West A, Nishimune Y, Morita T (1996) The mouse and human homologs of DMC1, the yeast meiosis-specific homologous recombination gene, have a common unique form of exon-skipped transcript in meiosis. Nucleic Acids Res 24:470–477

    Article  CAS  PubMed  Google Scholar 

  • He Z, Henricksen LA, Wold MS, Ingles CJ (1995) RPA involvement in the damage-recognition and incision steps of nucleotide excision repair. Nature 374:566–569

    Article  CAS  PubMed  Google Scholar 

  • Heyting C, Moens PB, van Raamsdonk W, Dietrich AJJ, Vink ACG, Redeker EJW (1987) Identification of two major components of the lateral elements of synaptonemal complexes of the rat. Eur J Cell Biol 43:148–154

    CAS  PubMed  Google Scholar 

  • Hunt PA, Hassold TJ (2002) Sex matters in meiosis. Science 296:2181–2183

    Article  CAS  PubMed  Google Scholar 

  • James RD, Schmiesing JA, Peters AH, Yokomori K, Disteche CM (2002) Differential association of SMC1 alpha and SMC3 proteins with meiotic chromosomes in wild-type and SPO11-deficient male mice. Chromosome Res 10:549–560

    Article  CAS  PubMed  Google Scholar 

  • Johnson J, Canning J, Kaneto T, Pru JK, Tilly JL (2004) Germline stem cells and follicular renewal in the postnatal mammalian ovary. Nature 428(6979):145–150

    Article  CAS  PubMed  Google Scholar 

  • Kneitz B, Cohen PE, Avdievich E, Zhu L, Kane MF, Hou H Jr, Kolodner RD, Kucherlapati R, Pollard JW, Edelmann W (2000) MutS homolog 4 localization to meiotic chromosomes is required for chromosome pairing during meiosis in male and female mice. Genes Dev 14:1085–1097

    CAS  PubMed  Google Scholar 

  • Kolas NK, Yuan L, Höög C, Heng HH, Marcon E, Moens PB (2004) Male mouse meiotic chromosome cores deficient in structural proteins SYCP3 and SYCP2 align by homology but fail to synapse and have possible impaired specificity of chromatin loop attachment. Cytogenet Genome Res 105:182–188

    Article  CAS  PubMed  Google Scholar 

  • Kwan KY, Moens PB, Wang JC (2003) Infertility and aneuploidy in mice lacking a type IA DNA topoisomerase III beta. Proc Natl Acad Sci U S A 100:2526–2531

    Article  CAS  PubMed  Google Scholar 

  • Makiniemi M, Hillukkala T, Tuusa J, Reini K, Vaara M, Huang D, Pospiech H, Majuri I, Westerling T, Makela TP et al (2001) BRCT domain-containing protein TopBP1 functions in DNA replication and damage response. J Biol Chem 276:30399–30406

    Article  CAS  PubMed  Google Scholar 

  • Matsuda Y, Moens PB, Chapman VM (1992) Deficiency of X and Y chromosomal pairing at meiotic prophase in spermatocytes of sterile interspecific hybrids between laboratory mice (Mus domesticus) and Mus spretus. Chromosoma 101:483–492

    Article  CAS  PubMed  Google Scholar 

  • Miyamoto T, Hasuike S, Yogev L, Maduro MR, Ishikawa M, Westphal H, Lamb DJ (2003) Azoospermia in patients heterozygous for a mutation in SYCP3. Lancet 362:1714–1719

    Article  CAS  PubMed  Google Scholar 

  • Moens PB, Freire R, Tarsounas M, Spyropoulos B, Jackson SP (2000) Expression and nuclear localization of BLM, a chromosome stability protein mutated in Bloom’s syndrome, suggest a role in recombination during meiotic prophase. J Cell Sci 113:663–672

    CAS  PubMed  Google Scholar 

  • Moens PB, Kolas NK, Tarsounas M, Marcon E, Cohen PE, Spyropoulos B (2002) The time course and chromosomal localization of recombination-related proteins at meiosis in the mouse are compatible with models that can resolve the early DNA–DNA interactions without reciprocal recombination. J Cell Sci 115:1611–1622

    CAS  PubMed  Google Scholar 

  • Pelttari J, Hoja MR, Yuan L, Liu JG, Brundell E, Moens P, Santucci-Darmanin S, Jessberger R, Barbero JL, Heyting C et al (2001) A meiotic chromosomal core consisting of cohesin complex proteins recruits DNA recombination proteins and promotes synapsis in the absence of an axial element in mammalian meiotic cells. Mol Cell Biol 21:5667–5677

    Article  CAS  PubMed  Google Scholar 

  • Perera D, Perez-Hidalgo L, Moens PB, Reini K, Lakin N, Syvaoja JE, San-Segundo PA, Freire R (2004) TopBP1 and ATR colocalization at meiotic chromosomes: role of TopBP1/Cut5 in the meiotic recombination checkpoint. Mol Biol Cell 15:1568–1579

    Article  CAS  PubMed  Google Scholar 

  • Pittman DL, Cobb J, Schimenti KJ, Wilson LA, Cooper DM, Brignull E, Handel MA, Schimenti JC (1998) Meiotic prophase arrest with failure of chromosome synapsis in mice deficient for Dmc1, a germline-specific RecA homolog. Mol Cell 1:697–705

    Article  CAS  PubMed  Google Scholar 

  • Reini K, Uitto L, Perera D, Moens PB, Freire R, Syvaoja JE (2004) TopBP1 localises to centrosomes in mitosis and to chromosome cores in meiosis. Chromosoma 112:323–330

    Article  CAS  PubMed  Google Scholar 

  • Rodriguez TA, Burgoyne PS (2000) Evidence that sex chromosome asynapsis, rather than excess Y gene dosage, is responsible for the meiotic impairment of XYY mice. Cytogenet Cell Genet 89:38–43

    Google Scholar 

  • Rodriguez TA, Burgoyne PS (2001) Spermatogenic failure in male mice with four sex chromosomes. Chromosoma 110:124–129

    CAS  PubMed  Google Scholar 

  • Roosen-Runge EC (1962) The process of spermatogenesis in mammals. Biol Rev Camb Philos Soc 37:343–377

    CAS  PubMed  Google Scholar 

  • Solari AJ, Rey Valzacchi G (1997) The prevalence of a YY synaptonemal complex over XY synapsis in an XYY man with exclusive XYY spermatocytes. Chromosome Res 5:467–474

    Article  CAS  PubMed  Google Scholar 

  • Tarsounas M, Morita T, Pearlman RE, Moens PB (1999) RAD51 and DMC1 form mixed complexes associated with mouse meiotic chromosome cores and synaptonemal complexes. J Cell Biol 147:207–220

    Article  CAS  PubMed  Google Scholar 

  • Turner JM, Aprilikova O, Xu X, Wang R, Kim S, Chandramouli GV, Barret JC, Burgoyne PS, Deng CX (2004) BRCA1, Histone H2AX phosphorylation, and male meiotic sex chromosome inactivation. Curr Biol 14:2135–2142

    Article  CAS  PubMed  Google Scholar 

  • Xu X, Aprelikova O, Moens P, Deng CX, Furth PA (2003) Impaired meiotic DNA-damage repair and lack of crossing-over during spermatogenesis in BRCA1 full-length isoform deficient mice. Development 130:2001–2012

    Article  CAS  PubMed  Google Scholar 

  • Yogev L, Gamzu R, Paz G, Kleiman S, Botchan A, Hauser R, Yavetz H (2002) Rate of homologous chromosome bivalents in spermatocytes may predict completion of spermatogenesis in azoospermic men. Hum Genet 110:30–35

    Article  CAS  PubMed  Google Scholar 

  • Yuan L, Liu JG, Zhao J, Brundell E, Daneholt B, Höög C (2000) The murine SCP3 gene is required for synaptonemal complex assembly, chromosome synapsis, and male fertility. Mol Cell 5:73–83

    Article  CAS  PubMed  Google Scholar 

  • Yuan L, Liu JG, Hoja MR, Wilbertz J, Nordqvist K, Höög C (2002) Female germ cell aneuploidy and embryo death in mice lacking the meiosis-specific protein SCP3. Science 296:1115–1118

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank Karen Rethoret for assistance with electron microscopy, Rolf Jessberger and K. Yokomori for antibodies to cohesins. The research was supported by a Discovery Grant from NSERC to P.B.M. and a studentship to E.M.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Peter B. Moens.

Additional information

Communicated by E.A. Nigg

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kolas, N.K., Marcon, E., Crackower, M.A. et al. Mutant meiotic chromosome core components in mice can cause apparent sexual dimorphic endpoints at prophase or X–Y defective male-specific sterility. Chromosoma 114, 92–102 (2005). https://doi.org/10.1007/s00412-005-0334-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00412-005-0334-8

Keywords

Navigation