RESUMO
Organisation of chromosome territories in interphase nuclei has been studied in many systems and positional alterations have been associated with disease phenotypes (e.g. laminopathies, cancer) in somatic cells. Altered nuclear organisation is also reported in developmental processes such as mammalian spermatogenesis where a "chromocentre" model is proposed with the centromeres and sex chromosomes repositioning to the nuclear centre. The purpose of this study was to test the hypothesis that alterations in nuclear organisation of human spermatozoa are associated with defects upstream in spermatogenesis (as manifest in certain infertility phenotypes). The nuclear address of (peri-) centromeric loci for 18 chromosomes (1-4, 6-12, 15-18, 20, X and Y) was assayed in 20 males using established algorithms for 3D extrapolations of 2D data. The control group comprised 10 fertile sperm donors while the test group was 10 patients with severely compromised semen parameters including high sperm aneuploidy. All loci examined in the control group adopted defined, interior positions thus providing supporting evidence for the presence of a chromocentre and interior sex chromosome territories. In the test group however there were subtle alterations in the nuclear address for certain centromeres in individual patients and, when all patient results were pooled, some different nuclear addresses were observed for chromosomes 3, 6, 12 and 18. Considering the extensive impairment of spermatogenesis in the test group (evidenced by compromised semen parameters and increased chromosome abnormalities), the observed differences in nuclear organisation for centromeric loci compared to the controls were modest. A defined pattern of nuclear reorganisation of centromeric loci in sperm heads therefore appears to be a remarkably robust process, even if spermatogenesis is severely compromised.
