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Alteration of nuclear architecture in male germ cells of chromosomally derived subfertile mice

¹ Dipartimento di Biologia Animale, Laboratorio di Biologia dello Sviluppo e Centro di Eccellenza in Biologia Applicata, Universita’ di Pavia, Piazza Botta, 9 – 27100 Pavia, Italy
² Dipartimento di Medicina Sperimentale, Sezione di Istologia ed Embriologia, Universita’ di Parma, Via Volturno, 39 – 43100 Parma, Italy
³ Department of Obstetrics and Gynaecology, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905, USA
⁴ Laboratorio de Cariobiología y Citogenética, Programa de Genética Humana, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Casilla 70061, Santiago 7, Chile
⁵ Dipartimento di Biologia Animale e dell’Uomo, Universita’ "La Sapienza" Roma, Via Alfonso Borelli, 50 – 00161 Roma, Italy

Author for correspondence (e-mail: silvia.garagna{at}unipv.it)

Accepted September 7, 2001

The mammalian cell nucleus consists of numerous compartments involved in the regular unfolding of processes such as DNA replication and transcription, RNA maturation, protein synthesis and cell division. Knowledge is increasing of the relationships between high-order levels of chromatin organization and its spatial organization, and of how these relationships contribute to the various functions carried out in the nucleus. We have studied the spatial arrangement of mouse telocentric chromosomes 5, 11, 13, 15, 16 and 17, some of their metacentric Robertsonian derivatives, and X and Y chromosomes by whole chromosome painting in male germ (spermatogonia, pachytene spermatocytes and spermatids) and Sertoli cells of homozygous and heterozygous individuals. Using dual-colour fluorescence in situ hybridization we found that these chromosomes occupy specific nuclear territories in each cell type analysed. When chromosomes are present as Robertsonian metacentrics in the heterozygous state, that is, as Robertsonian metacentrics and their homologous telocentrics, differences in their nuclear positions are detectable: heterozygosity regularly produces a change in the nuclear position of one of the two homologous telocentrics in all the cell types studied. In the Robertsonian heterozygotes, the vast majority of the Sertoli cells show the sex chromosomes in a condensed state, whereas they appear decondensed in the Robertsonian homozygotes. As the Robertsonian heterozygosities we studied produce a chromosomally derived impairment of male germ-cell differentiation, we discuss the possibility that changes in chromosome spatial territories may alter some nuclear machinery (e.g., synapsis, differential gene expression) important for the correct unfolding of the meiotic process and for the proper functioning of Sertoli cells.

Key words: Nuclear architecture, Germ cells, Chromosome translocation, Subfertile mice, Sertoli cell, X and Y chromosomes