Apoptosis in Spermiogenesis of Multiple Robertsonian Heterozygotes of Mus musculus domesticus

Apoptosis in Spermiogenesis of Multiple Robertsonian Heterozygotes of Mus musculus domesticus

Main Article Content

Marisel González
Raúl Fernández-Donoso
Soledad Berríos

Abstract

Mus musculus domesticus is a species that is characterized by a diploid number of 40 chromosomes, all telocentrics (acrocentrics). In natural populations of Mus with high frequency Robertsonian chromosome translocations (RBs), a fusion at centromere-level between two autosomal telocentric, producing metacentric Rb chromosomes and a variety of natural subspecies with diploid chromosome numbers below 40. Rb chromosomes do not affect the viability of individuals but mainly fertility of Rb heterozygotes. In their meiosis the metacentric Rb and the homologous telocentrics form trivalents that have problems in synapsis and segregation. This paper presents a comparative analysis of spermatogenesis considering the stages of the epithelium and the number of germ cells loss by apoptosis comparing heterozygote males 2n=32, carriers 8 trivalents, and homozygotes 2n=40 and 2n=24. It was found that the number of spermatocytes in first prophase was similar in the different seminiferous epithelium stages in all the chromosome constitutions. In the 2n=32 heterozygotes a significant decreased number of spermatids was reflected in the proportion of spermatocytes and spermatids that was 1:1.7. In the homozygote males rare germ cell in apoptosis (positive for caspase 3) were observed, which were mainly concentrated in the XII stage of the seminiferous epithelium. In heterozygote spermatocytes apoptotic germ cell number was significantly higher than that registered in homozygote males, and generally correspond to spermatocytes in meiotic divisions. This selective removal of cells possibly carrying anomalies, either in chromosome alignment or segregation, is consistent with the smaller number of spermatids and the relative sub-fertility observed in 2n=32 Rb heterozygotes.

References

Abercrombie, M. Estimation of nuclear population from microtome sections. Anat. Rec., 94:239-47, 1946.

Anahory, T.; Hamamah, S.; Andréo, B.; Hédon, B.; Claustres, M.; Sarda, P. & Pellestor, F. Sperm segregation analysis of a (13;22) Robertsonian translocation carrier by FISH: a comparison of locusspecific probe and whole chromosome painting. Hum. Reprod., 20(7):1850-4, 2005.

Anton, E.; Blanco, J.; Egozcue, J. & Vidal, F. Sperm FISH studies in seven male carriers of Robertsonian translocation t(13;14)(q10;q10). Hum. Reprod., 19(6):1345-51, 2004.

Barchi, M.; Mahadevaiah, S.; Di Giacomo, M.; Baudat, F.; de Rooij, D. G.; Burgoyne, P. S.; Jasin, M. & Keeney, S. Surveillance of different recombination defects in mouse spermatocytes yields distinct responses despite elimination at an identical developmental stage. Mol. Cell Biol., 25(16):7203-15, 2005.

Berríos, S.; Manieu, C.; López-Fenner, J.; Ayarza, E.; Page, J.; González, M.; Manterola, M. & Fernández-Donoso, R. Robertsonian chromosomes and the nuclear architecture of mouse meiotic prophase spermatocytes. Biol. Res., 47:16, 2014.

Borg, C. L.; Wolski, K. M.; Gibbs, G. M. & O’Bryan, M. K. Phenotyping male infertility in the mouse: how to get the most out of a 'non-performer'. Hum. Reprod. Update, 16(2):205-24, 2010.

Burgoyne, P. S.; Mahadevaiah, S. K. & Turner, J. M. The consequences of asynapsis for mammalian meiosis. Nat. Rev. Genet., 10(3):207-16, 2009.

Castiglia, R. & Capanna, E. Contact zone between chromosomal races of Mus musculus domesticus. 2. Fertility and segregation in laboratory-reared and wild mice heterozygous for multiple robertsonian rearrangements. Heredity (Edinb.), 85(Pt. 2):147-56,2000.

Cohen, P. E.; Pollack, S. E. & Pollard, J. W. Genetic analysis of chromosome pairing, recombination, and cell cycle control during first meiotic prophase in mammals. Endocr. Rev., 27(4):398-426, 2006.

de Rooij, D. G & de Boer, P. Specific arrests of spermatogenesis in genetically modified and mutant mice. Cytogenet. Genome Res., 103(3-4):267-76, 2003.

Eaker, S.; Pyle, A.; Cobb, J. & Handel, M. A. Evidence for meiotic spindle checkpoint from analysis of spermatocytes from Robertsonian-chromosome heterozygous mice. J. Cell Sci., 114(Pt. 16):2953-65, 2001.

Fernández-Donoso, R. La arquitectura del núcleo y los reordenamientos cromosómicos en los mamíferos. Museo Nacional de Historia Natural, Publicación Ocasional, 38:165-95, 1982.

Garagna, S.; Zuccotti, M.; Thornhill, A.; Fernandez-Donoso, R.; Berrios, S.; Capanna, E. & Redi, C. A. Alteration of nuclear architecture in male germ cells of chromosomally derived subfertile mice. J. Cell Sci., 114(Pt. 24):4429-34, 2001.

Garagna, S.; Page, J.; Fernandez-Donoso, R.; Zuccotti, M. & Searle, J. B. The Robertsonian phenomenon in the house mouse: mutation, meiosis and speciation. Chromosoma, 123(6):529-44, 2014.

Hauffe, H. C. & Searle, J. B. Chromosomal heterozygosity and fertility in house mice (Mus musculus domesticus) from Northern Italy. Genetics, 150(3):1143-54, 1998.

Hamer, G.; Novak, I.; Kouznetsova, A. & Höög, C. Disruption of pairing and synapsis of chromosomes causes stage-specific apoptosis of male meiotic cells. Theriogenology, 69(3):333-9, 2008.

King, M. Species Evolution: The Role of Chromosome Change. New York, Cambridge University Press, 1993.

Lee, N. P.; Leung, K. W.; Wo, J. Y.; Tam, P. C.; Yeung, W. S. & Luk, J. M. Blockage of testicular connexins induced apoptosis in rat seminiferous epithelium. Apoptosis, 11(7):1215-29, 2006.

McManus, J. F. Histological demonstration of mucin after periodic acid. Nature, 158:202, 1946.

Manieu, C.; González, M.; López-Fenner, J.; Page, J.; Ayarza, E.; Fernández-Donoso, R. & Berríos, S. Aneuploidy in spermatids of Robertsonian (Rb) chromosome heterozygous mice. Chromosome Res., 22(4):545-57, 2014.

Manterola, M.; Page, J.; Vasco, C.; Berrios, S.; Parra, M.T.; Viera, A.; Rufas, J. S.; Zuccotti, M.; Garagna, S. & Fernández-Donoso, R. A high incidence of meiotic silencing of unsynapsed chromatin is not associated with substantial pachytene loss in heterozygous male mice carrying multiple simple robertsonian translocations. PLoS Genet., 5(8):e1000625, 2009.

Medarde, N.; Merico, V.; López-Fuster, M. J.; Zuccotti, M.; Garagna , S. & Ventura, J. Impact of the number of Robertsonian chromosomes on germ cell death in wild male house mice. Chromosome Res., 23(2):159-69, 2015.

Merico, V.; Pigozzi, M. I.; Esposito, A.; Merani, M. S. & Garagna, S. Meiotic recombination and spermatogenic impairment in Mus musculus domesticus carrying multiple simple Robertsonian translocations. Cytogenet. Genome Res., 103(3-4):321-9, 2003.

Merico, V.; de Barboza, G. D.; Vasco, C.; Ponce, R.; Rodriguez, V.; Garagna, S. & Tolosa de Talamoni, N. A mitochondrial mechanism is involved in apoptosis of Robertsonian mouse male germ cells. Reproduction, 135(6):797-804, 2008.

Moradkhani, K.; Puechberty, J.; Bhatt, S.; Lespinasse, J.; Vago, P.; Lefort, G.; Sarda, P.; Hamamah, S. & Pellestor, F. Rare Robertsonian translocations and meiotic behaviour: sperm FISH analysis of t(13;15)and t(14;15) translocations: a case report. Human Reprod., 21(12):3193-8, 2006.

Odorisio, T.; Rodriguez, T. A.; Evans, E. P.; Clarke, A. R. & Burgoyne, P. S. The meiotic checkpoint monitoring synapsis eliminates spermatocytes via p53- independent apoptosis. Nat. Genet., 18(3):257-61,1998.

Piálek, J.; Hauffe, H. C. & Searle, J. B. Chromosomal variation in the house mouse. Biol. J. Linn. Soc., 84(3):535-63, 2005.

Rieseberg, L. H. Chromosomal rearrangements and speciation. Trends Ecol. Evol., 16(7):351-8, 2001.

Russell, L. D.; Sinha Hikim, A. P. & Ettlin, R. Histological and Histopathological Evaluation of the Testis. St. Louis, Cache River Press, 1990.

Sans-Fuentes, M. A.; García-Valero, J.; Ventura, J. & LópezFuster, M. J. Spermatogenesis in house mouse in a Robertsonian polymorphism zone. Reproduction, 140(4):569-81, 2010.

Shaha, C.; Tripathi, R. & Mishra, D. P. Male germ cell apoptosis: regulation and biology. Philos. Trans. R. Soc. Lond. B Biol. Sci., 365(1546):1501-15, 2010.

Sinha Hikim, A. P. & Swerdloff, R. S. Hormonal and genetic control of germ cell apoptosis in the testis. Rev. Reprod., 4(1):38-47,1999.

Turner, J. M.; Mahadevaiah, S. K.; Fernández-Capetillo, O.; Nussenzweig, A.; Xu, X.; Deng, C. X. & Burgoyne, P. S. Silencing of unsynapsed meiotic chromosomes in the mouse. Nat. Genet., 37(1):41-7, 2005.

Turner, L. M.; Schwahn, D. J. & Harr, B. Reduced male fertility is common but highly variable in form and severity in a natural house mouse hybrid zone. Evolution, 66(2):443-58, 2012.

Wallace, B. M.; Searle, J. B. & Everett, C. A. The effect of multiple simple Robertsonian heterozygosity on chromosome pairing and fertility of wild-stock house mice (Mus musculus domesticus). Cytogenet. Genome Res., 96(1-4):276-86, 2002.

Zhuang, X.; Huang, J.; Jin, X.; Yu, Y.; Li, J.; Qiao, J. & Liu, P. Chromosome aberrations and spermatogenic disorders in mice with Robertsonian translocation (11; 13). Int. J. Clin. Exp. Pathol., 7(11):7735-43, 2014.