ABSTRACT
Studies of nuclear organisation, most commonly determining the nuclear location of chromosome territories and individual loci, have furthered our understanding of nuclear function, differentiation and disease. In this study, by examining eight loci on different chromosomes, we tested hypotheses that: (1) totipotent human blastomeres adopt a nuclear organisation akin to that of committed cells; (2) nuclear organisation is different in chromosomally abnormal blastomeres; and (3) human blastomeres adopt a ;chromocentre' pattern. Analysis of in vitro fertilisation (IVF) conceptuses permits valuable insight into the cell biology of totipotent human nuclei. Here, extrapolations from images of preimplantation genetic screening (PGS) cases were used to make comparisons between totipotent blastomeres and several committed cells, showing some differences and similarities. Comparisons between chromosomally abnormal nuclei and those with no detected abnormality (NDA) suggest that the former display a significant non-random pattern for all autosomal loci, but there is a less distinct, possibly random, pattern in 'NDA' nuclei. No evidence was found that the presence of an extra chromosome is accompanied by an altered nuclear location for that chromosome. Centromeric loci on chromosomes 15 and 16 normally seen at the nuclear periphery were mostly centrally located in aneuploid cells, providing some evidence of a 'chromocentre'; however, the chromosome-18 centromere was more peripheral, similar to committed cells. Our results provide clues to the nature of totipotency in human cells and might have future applications for preimplantation diagnosis and nuclear transfer.
Subject(s)
Blastocyst/cytology , Cell Nucleus/ultrastructure , Chromosome Aberrations/embryology , Chromosomes/ultrastructure , Totipotent Stem Cells/cytology , Aneuploidy , Blastocyst/metabolism , Blastomeres/cytology , Blastomeres/metabolism , Cell Differentiation/genetics , Cell Lineage/genetics , Cell Nucleus/genetics , Cell Nucleus/metabolism , Cells, Cultured , Centromere/genetics , Centromere/metabolism , Centromere/ultrastructure , Chromosome Mapping/methods , Chromosomes/genetics , Chromosomes/metabolism , Chromosomes, Human, Pair 15/genetics , Chromosomes, Human, Pair 15/metabolism , Chromosomes, Human, Pair 15/ultrastructure , Chromosomes, Human, Pair 16/genetics , Chromosomes, Human, Pair 16/metabolism , Chromosomes, Human, Pair 16/ultrastructure , Chromosomes, Human, Pair 18/genetics , Chromosomes, Human, Pair 18/metabolism , Chromosomes, Human, Pair 18/ultrastructure , Cytogenetic Analysis , Embryonic Development/genetics , Humans , Male , Totipotent Stem Cells/metabolism , Tumor Cells, CulturedABSTRACT
Despite the difficulties in determining the relative maternal vs. paternal contributions to infertility it is often suggested that a male factor problem is implicated in 50% of cases. This review is concerned specifically with male fertility disorders that have a clearly defined genetic component. The genetic causes of infertility can be broken down into Y chromosome deletions (specifically deletions in the AZF a, b, and c regions), single gene disorders (particularly those relating to the CFTR gene), multifactorial causes and chromosome abnormalities. Chromosome abnormalities can be numerical (such as trisomy--full blown or mosaic) or structural (such as inversions or translocations). Of especial interest at present is the incidence of levels of numerical chromosome abnormalities in the sperm of infertile men; prospects for screening sperm for such abnormalities are discussed.
