Accumulation of numerical and structural chromosome imbalances in spermatozoa from reciprocal translocation carriers

Abstract

Is there a relationship between the occurrence of specific segregation modes and the production of additional numerical abnormalities in spermatozoa from reciprocal translocation carriers? The production of aneuploid and diploid spermatozoa tends to be associated with an unbalanced segregation outcome of the rearranged chromosomes. Carriers of reciprocal translocations have an increased genetic reproductive risk as a consequence of producing higher numbers of unbalanced spermatozoa. These imbalances can originate during the segregation of the rearranged chromosomes and also from the occurrence of interchromosomal effects (ICEs). Usually, the outcome of both events is studied independently by means of sperm fluorescent in situ hybridization (FISH). We designed a sequential FISH protocol based on two successive hybridization rounds to study the segregation outcome of the rearranged chromosomes and the presence of additional numerical abnormalities in the same sperm nuclei. The study was performed between February 2010 and February 2012. Sperm samples from eight reciprocal translocation carriers were processed for FISH analysis. Numerical abnormalities for chromosomes X, Y, 13, 18 and 21 were evaluated in the first hybridization round. The aneuploid and diploid nuclei were relocated and analysed for the segregation outcome of the rearranged chromosomes in the second hybridization round. In every carrier, another population of non-selected spermatozoa was also analysed with the aim of defining the general segregation outcome of each reorganization event. Overall, the selected population of aneuploid and diploid spermatozoa showed significant increased frequencies of unbalanced segregation modes of the rearranged chromosomes (3:1, 4:0 and 'other') when compared with the non-selected population of spermatozoa. A P-value of <0.05 was chosen to determine if differences observed were statistically significant. FISH only allows the analysis of a limited number of chromosomes. Information about the content of additional chromosomes would have been useful in order to broaden the number of aneuploid spermatozoa population, and to infer a more accurate possible mechanism for generating chromosomal imbalances. There was no previous data about a relationship between chromosomal numerical abnormalities and segregation of rearranged chromosomes. Our findings are consistent with a possible gathering of chromosomal abnormalities in a given nucleus. This information can be used towards a better understanding of the meiotic mechanisms involved in non-disjunction events in gametes from reciprocal translocation carriers. Also, it would help to provide a better reproductive genetic risk assessment in these patients. This work was supported by funding of projects SAF2010-2241 (Ministerio de Ciencia e Innovación, Spain), SGR2009-282 (Generalitat de Catalunya, Spain) and UAB CF-180034 (Universitat Autònoma de Barcelona, Spain). The authors declare the lack of competing interests in this study.