We quantitatively analyzed the spermatogenic process, including evaluation of seminiferous tubules with defective cycles, rates of germ cell death and sperm morphology, in adult male mice with standard telocentric chromosomes (2n = 40, CD1 strain), homozygous (2n = 24, Mil II population) and heterozygous (2n = 24 × 40) for Robertsonian (Rb) rearrangements. The animals were analyzed at three different ages: three, five and seven months after birth. The number and position of crossover events were also determined by chiasmata counting and immunostaining with an antibody against mouse MLH1 protein. Our analysis of spermatogenesis confirms the impairment of the spermatogenic process in multiple simple heterozygotes due to both germ cell and abnormal sperm morphology. The detrimental effects exerted by Rb heterozygosities were found to be at least partially buffered with time: the frequency of defective tubules was lower and germ cell survival and sperm morphology better in 7-month-old animals than in the 3- and 5-month-old mice. While there are previously published data on germ cell death in multiple simple heterozygotes, this is the first report of a partial rescue of spermatogenesis with time. The mean frequency of MLH1 foci was lower in Rb homozygous and heterozygous mice than in mice carrying all telocentric chromosomes. The lower number of foci in Rb mice can be ascribed to a decrease in the number of multiple chiasmata and the maintenance of single chiasmata preferentially located in the terminal region of both the telocentric and metacentric chromosomes.   

1.
Abercrombie M: Estimation of nuclear population from microtome sections. Anat Rec 94:239–247 (1946).
2.
Anderson LK, Reeves A, Webb LM, Ashley T: Distribution of crossing over on mouse synaptonemal complexes using immunofluorescent localization of MLH1 protein. Genetics 151:1569–1579 (1999).
3.
Baccetti B, Capitani S, Collodel G, Estenoz M, Gambera L, Piomboni P: Infertile spermatozoa in human carrier of Robertsonian translocation 14;22. Fert Steril 78:1127–1130 (2002).
4.
Baker SM, Plug AW, Prolla TA, Bronner CE, Harris AC, Yao X, Christie DM, Monell C, Arnheim M, Braley A, Ashley T, Liskay RM: Involvement of mouse Mlh1 in DNA mismatch repair and meiotic crossing over. Nature Genet 13:336–342 (1996).
5.
Barlow AL, Hulten MA: Crossing over analysis at pachytene in man. Eur J hum Genet 6:350–358 (1998).
6.
Bhasin S, Mallidis C, Ma K: The genetic basis of infertility in men, in Holly JMP, Wu FCW (eds): Clinical endocrinology and metabolism, vol 14, pp 363–388 (Harcourt Publishers Ltd, London 2000).
7.
Bidau C, Gimenez MD, Palmer CL, Searle JB: The effects of Robertsonian fusions on chiasma frequency and distribution in the house mouse (Mus musculus domesticus) from a hybrid zone in northern Scotland. Heredity 87:305–313 (2001).
8.
Britton-Davidian J, Catalan J, da Graca Ramalhinho M, Ganem G, Auffray JC, Capela R, Biscoito M, Searle JB, da Luz Mathias M: Rapid chromosomal evolution in island mice. Nature 403:158 (2000).
9.
Bruce WR, Furrer R, Wyrobek AJ: Abnormalities in the shape of murine sperm after acute testicular X-irradiation. Mutat Res 23:381–386 (1974).
10.
Brugh VM 3rd, Maduro MR, Lamb DJ: Genetic disorders and infertility. Urol Clin North Am 30:143–152 (2003).
11.
Bryan JHD: An eosin-fast green-naphthol yellow mixture for differential staining of the cytologic components in mammalian spermatozoa. Stain Technol 45:231–236 (1970).
12.
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 85:147–156 (2000).
13.
Castiglia R, Capanna E: Chiasma repatterning across a chromosomal hybrid zone between chromosomal races of Mus musculus domesticus. Genetica 114:35–40 (2002).
14.
Davisson MT, Akeson EC: Recombination suppression by heterozygous Robertsonian chromosomes in the mouse. Genetics 133:649–667 (1993).
15.
Dumas D, Britton-Davidian J: Chromosomal rearrangements and evolution of recombination: comparison of chiasma distribution patterns in standard and Robertsonian populations of the house mouse. Genetics 162:1355–1366 (2002).
16.
Eaker S, Pyle A, Cobb J, Handel MA: Evidence for meiotic spindle checkpoint from analysis of spermatocytes from Robertsonian-chromosome heterozygous mice. J Cell Sci 114:2953–2965 (2001).
17.
Eddy EM: Male germ cell gene expression. Recent Prog Horm Res 57:103–128 (2002).
18.
Evans EP, Breckon G, Ford CE: An air drying method for meiotic preparations from mammalian testes. Cytogenetics 3:289–294 (1964).
19.
Feng HL: Molecular biology of male infertility. Archs Androl 49:19–27 (2003).
20.
Forejt J: X-Y involvement in male sterility caused by autosome translocations. A hypothesis, in Crosignani PG, Rubin BL, Fraccaro M (eds): Genetic Control of Gamete Production and Function, vol 3, pp 135–151 (Academic Press, New York 1982).
21.
Forejt J: X-inactivation and its role in male sterility. Chrom Today 8:117–127 (1984).
22.
Froenicke L, Anderson LK, Wienberg J, Ashley T: Male mouse recombination maps for each autosome identified by chromosome painting. Am J hum Genet 71:1353–1368 (2002).
23.
Gabriel-Robez O, Rumpler Y: The meiotic pairing behaviour in human spermatocytes carrier of chromosome anomalies and their repercussions on reproductive fitness. II. Robertsonian and reciprocal translocations. A European collaborative study. Annls Génét 39:17–25 (1996).
24.
Garagna S, Redi CA, Zuccotti M, Britton-Davidian J, Winking H: Kinetics of oogenesis in mice heterozygous for Robertsonian translocation. Differentiation 42:167–171 (1990).
25.
Garagna S, Broccoli D, Redi CA, Searle JB, Cooke HJ, Capanna E: Robertsonian metacentrics of the house mouse lose telomeric sequences but retain some minor satellite DNA in the pericentromeric area. Chromosoma 103:685–692 (1995).
26.
Garagna S, Marziliano N, Zuccotti M, Searle JB, Capanna E, Redi CA: Pericentromeric organization at the fusion point of mouse Robertsonian translocation chromosomes. Proc natl Acad Sci, USA 98:171–175 (2001).
27.
Gosden RG, Richardson DW, Brown N, Davidson DW: Structure and gametogenic potential of seminiferous tubules in ageing mice. J Reprod Fertil 64:127–133 (1982).
28.
Gropp A, Winking H: Robertsonian translocation: cytology, meiosis, segregation pattern and biological consequences of heterozygosity, in Berry RJ (ed): Biology of the House Mouse, vol 47, pp 141–181 (Academic Press, London 1981).
29.
Gropp A, Winking H, Redi CA, Capanna E, Britton-Davidian J, Noack G: Robertsonian karyotype variation in wild house mice from Rhaeto-Lombardia. Cytogenet Cell Genet 34:67–77 (1982).
30.
Giwercman A, Bonde JP: Declining male fertility and environmental factors. Endocrinol Metab North Am 27:807–830 (1998).
31.
Hacker-Klom UB: Age dependence of murine spermatogenesis. Z Naturforsch [C] 50:303–310 (1995).
32.
Hauffe HC, Searle JB: Chromosomal heterozygosity and fertility in house mice (Mus musculus domesticus) from Northern Italy. Genetics 150:1143–1154 (1998).
33.
Honda H, Miharu N, Samura O, He H, Ohama K: Meiotic segregation analysis of a 14;21 Robertsonian translocation carrier by fluorescence in situ hybridization. Hum Genet 106:188–193 (2000).
34.
Hotta Y, Chandley AC: Activities of X-linked enzymes in spermatocytes of mice rendered sterile by chromosomal alterations. Gamete Res 6:65 (1982).
35.
Jagiello G, Fang JS: Analyses of diplotene chiasma frequencies in mouse oocytes and spermatocytes in relation to ageing and sexual dimorphism. Cytogenet Cell Genet 23:53–60 (1979).
36.
John B, King M: The interrelationship between heterochromatin distribution and chiasma distribution. Genetica 66:183–194 (1985).
37.
Johannisson R, Winking H: Synaptonemal complexes of chains and rings in mice heterozygous for multiple Robertsonian translocations. Chrom Res 2:137–145 (1994).
38.
Kashiwabara S, Noguchi J, Zhuang T, Ohmura K, Honda A, Sugiura S, Miyamoto K, Takahashi S, Inoue K, Oguru A, Baba T: Regulation of spermatogenesis by testis-specific, cytoplasmic Poly(A) Polymerase TPAP. Science 298:1999–2002 (2002).
39.
Koehler KE, Millie EA, Cherry JP, Burgoyne PS, Evans EP, Hunt PA, Hassold TJ: Sex-specific differences in meiotic chromosome segregation revealed by dicentric bridge resolution in mice. Genetics 62:1367–1379 (2002).
40.
Leblond CP, Clermont Y: Spermiogenesis of rat, mouse, hamster and guinea-pigs as revealed by the “periodic acid-fuchsin sulphurus acid” technique. Am J Anat 90:167–215 (1952).
41.
Lifschytz E, Lindsley DL: The role of X-chromosome inactivation during spermatogenesis (Drosophila-allocycly-chromosome evolution-male sterility-dosage compensation). Proc natl Acad Sci, USA 69:182–186 (1972).
42.
Matzuk MM, Lamb DJ: Genetic dissection of mammalian fertility pathways. Nature Cell Biol 4 (Suppl):s41–s49 (2002).
43.
McLachlan RI: The endocrine control of spermatogenesis, in Holly JMP, Wu FCW (eds): Clinical Endocrinology and Metabolism, vol 14, pp 345–362 (Harcourt Publishers Ltd, London 2000).
44.
Moses MJ: New cytogenetic studies on mammalian meiosis, in Serio M, Martini L (eds): Animal Models in Human Reproduction, pp 169–190 (Raven Press, New York 1980).
45.
Nicklas RB: How cells get the right chromosomes. Science 275:632–637 (1997).
46.
Oakberg EF: A description of spermatogenesis in the mouse and its use in analysis of the cycle of the seminiferous epithelium and germ cell renewal. Am J Anat 99:391–413 (1956).
47.
Odorisio T, Rodriguez TA, Evans EP, Clarke AR, Burgoyne PS: The meiotic checkpoint monitoring synapsis eliminates spermatocytes via p53-independent apoptosis. Nature Genet 18:257–261 (1998).
48.
Peters AH, Plug AW, van Vugt MJ, de Boer P: A drying-down technique for the spreading of mammalian meiocytes from the male and female germline. Chrom Res 5:66–68 (1997).
49.
Polani PE, Jagiello GM: Chiasmata, meiotic univalents, and age in relation to aneuploid imbalance in mice. Cytogenet Cell Genet 16:505–529 (1976).
50.
Redi CA, Capanna E: Robertsonian heterozygotes in the house mouse and the fate of their germ cells, in Daniel A (ed): The Cytogenetics of Mammalian Autosomal Rearrangements, pp 315–359 (Liss, New York 1988).
51.
Redi CA, Hilscher B, Winking H: Stage-dependent enzymatic activities in spermatogenesis of mice with the standard karyotype and of chromosomal variants with impaired fertility. Andrologia 15:322–330 (1983).
52.
Redi CA, Garagna S, Hilscher B, Winking H: The effects of some Robertsonian chromosome combinations on the seminiferous epithelium of the mouse. J Embryol exp Morphol 85:1–19 (1985).
53.
Reeves A, Tear J: MicroMeasure for Windows, version 3.3 (http://www. colostate/edu/Depts/Biology/MicroMeasure) (2000).
54.
Safronova LD, Orlov VN: Behavior of pachytene chromosomes in male mice heterozygotic for various translocations (Rb(8,17), T(16,17)43H). Genetika 29:1014–1025 (1993).
55.
Said K, Saad A, Auffray JC, Britton-Davidian J: Fertility estimates in the Tunisian all-acrocentric and Robertsonian populations of the house mouse and their chromosomal hybrids. Heredity 71 (Pt 5):532–538 (1993).
56.
Scherthan H, Weich S, Schwegler H, Heyting C, Harle M, Cremer T: Centromere and telomere movements during early meiotic prophase of mouse and man are associated with the onset of chromosome pairing. J Cell Biol 134:1109–1125 (1996).
57.
Searle JB: Chromosomal hybrid zones in eutherian mammals, in Harrison RG (ed): Hybrid Zones and the Evolutionary Process, pp 507–532 (Oxford University Press, Oxford 1993).
58.
Sharpe RM: Environment, life style and male infertility, in Holly JMP, Wu FCW (eds): Clinical Endocrinology and Metabolism, vol 14, pp 489–503 (Harcourt Publishers Ltd, London 2000).
59.
Solari AJ: Synaptonemal complex analysis in human male infertility. Eur J Histochem 43:265–276 (1999).
60.
Sumner AT: A simple technique for demonstrating centromeric heterochromatin. Expl Cell Res 75:304–306 (1972).
61.
Sybenga J, Rickards GK: The orientation of multivalents at meiotic metaphases I: a workshop report. Genome 29:612–620 (1987).
62.
Tanemura K, Kurohmaru M, Kuramoto K, Hayashi Y: Age-related morphological changes in the testis of the BDF1 mouse. J vet med Sci 55:703–710 (1993).
63.
Tettenborg U, Gropp A: Meiotic nondisjunction in mice and mouse hybrids. Cytogenetics 9:272–283 (1970).
64.
Wallace BM, Searle JB, Everett CA: The effect of multiple simple Robertsonian heterozygosity on chromosome pairing and fertility of wild-stock house mice (Mus musculus domesticus). Cytogenet Genome Res 96:276–286 (2002).
65.
Winking H, Reuter C, Bostelmann H: Unequal nondisjunction frequencies of trivalent chromosomes in male mice heterozygous for two Robertsonian translocations. Cytogenet Cell Genet 91:303–306 (2000).
66.
Wirth-Dzieciolowska E, Czminska K: Longevity and aging of mice from lines divergently selected for body weight for over 90 generations. Biogerontology 1:171–178 (2000).
67.
Wyrobeck AJ, Heddle JA, Bruce WR: Chromosomal abnormalities and the morphology of mouse sperm heads. Can J Genet Cytol 17:675–681 (1975).
68.
Yamamoto M, Miklos GL: Genetic studies on heterochromatin in Drosophila melanogaster and their implications for the functions of satellite DNA. Chromosoma 66:71–98 (1978).
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