Chromosome anomalies in human lymphocytes, oocytes, zygotes and preimplantation embryos
Chromosome aberrations are very important in human life because they can lead to disease or death. They have three important dimensions, formation, transmission and effect. They may occur spontaneously or be induced by physical or chemical agents. Human reproductive failure is characterised by a high rate of spontaneous chromosome anomalies while chromosome aberrations in human cancers are in most cases induced. In a proliferating cell system chromosome aberrations may be eliminated or transmitted for one or more cell divisions. In the former case the daughter cells may revert to normality or may die, while in the latter case the abnormal situation is propagated or altered. Chromosome material which is eliminated at anaphase may be either entirely lost or form micronuclei. Such micronuclei are mainly formed from chromosome fragments but they can also be formed from whole chromosomes in a process called anaphase lagging. However, a considerable number of aberrations survive and are transmitted for at least one cell division. In the present study 55% of fragments in X-irradiated lymphocyte cultures were transmitted to the second cell division, 80% of the remainder were transmitted to the third cell division and 50% of the remainder were transmitted to the fourth cell division. Dicentric chromosomes showed even higher transmission frequencies. About 68% survived the first division, 89% of the remainder the second division and 70% of the remainder the third division. It has been suggested that the micronucleus test could perhaps replace in many case the metaphase analysis test if a quantitative and qualitative relationship could be established between the frequencies of aberrations and of micronuclei. However, no such relationship could be established between the two in the present study mainly because of the evident implication of numerical aberrations in the formation of micronuclei and the presence of perhaps several populations of cells in lymphocyte cultures, even though there was no real evidence to this in the present study. Similar kinds of chromosome aberrations were also observed in human oocytes and zygotes and preimplantation embryos. Structural aberrations, mainly chromosome fragmentation, were the most frequent in both cases. In the oocytes they were equalled in frequency by aneuploidy (20%) and were followed by diploidy (13%), while in the pre-embryos by mosaicism (9.7%), both euploid and aneuploid, and then by polyploidy (4.8%). The overall incidence of abnormal oocytes and zygotes was 57% and of pre-embryos 42%. Particularly interesting was the relatively high incidence of trisomic mosaicism in the pre-embryos and of hypohaploidy in the oocytes. Polyploidy in the pre-embryos seems to originate primarily from polyspermic fertilization and then due to the formation of diploid oocytes during oogenesis. Diploid spermatozoa do not seem to contribute to polyploidy because either they are not produced or they cannot achieve fertilization. Polyspermic oocytes do not always result in polyploid pre-embryos but often they result in mosaicism. Haploidy is infrequent in pre-embryos and it is possibly induced by the in vitro fertilization methods. Haploid pre-embryos are not likely to achieve implantation. Also interesting was the finding that trisomy may not be as frequent as it would be expected, mainly due to the presence of many other chromosome anomalies which are observed only at the preimplantation stages of embryogenesis. A major obstacle in the cytogenetic analysis of human pre-embryos is the frequently observed asynchrony in blastomere division. To overcome this problem either prolonged colcemid treatments must be used, which unfortunately reduce the quality of the chromosomes, or perhaps use the method of reversible DNA synthesis inhibition. This method was shown to improve the mitotic index when short colcemid treatments were used, yielding also good quality chromosomes, in mouse pre-embryos.