Sperm fluorescent in situ hybridisation study of interchromosomal effect in six Tunisian carriers of reciprocal and Robertsonian translocations

Abstract

Carriers of structural chromosomal anomalies, translocations and inversions are at increased risk of aneuploid gametes production. Besides the direct effect on the involved chromosomes, these rearrangements might disturb the segregation of other structurally normal chromosomes during meiosis. Such event is known as interchromosomal effect. In this study, six male carriers of translocations, four reciprocals and two Robertsonians, were investigated. In addition, seven fertile men with normal 46,XY karyotypes and normal sperm characteristics were enrolled as a control group. Spermatic fluorescent in situ hybridisation specific for chromosomes X, Y, 18, 21 and 22 was carried out. The Mann-Whitney U-test was used to compare the aneuploidy rates between patients and controls. All translocation carriers showed significantly increased frequencies of disomy of all investigated chromosomes, and diploid gametes compared with the control group (p < .05). However, disomy XY was not significantly different between controls and patients (p > .05). We have also observed a considerable interindividual variability in disomy and diploidy rates. These results confirm that the interchromosomal effect seems to exist and could contribute to higher rates of abnormal prenatal aneuploidy, resulting in a small increase in the risk of miscarriage and birth of children with congenital abnormalities and a potential reduction in fertility.

FISH analysis of numerical chromosomal abnormalities in the sperm of robertsonian translocation der(13; 14)(q10;q10) carriers

“…The frequency of disomy for 15 chromosomes (1-3, 5-7, 9, 11, 12, 15, 19, 21, 22, X, and Y) was significantly higher than that in normozoospermic men, with the highest frequency observed for disomy 21, followed by that for 19, 22, 5, the sex chromosomes, and chromosomes 2, 9, 1, 15, 3, 20, 12, 4, 6, and 11. Our results are consistent with those of previous studies analyzing the frequency of disomy for chromosomes 18, 21, X, and Y, all of which showed a significant increase in the frequency of disomy for the sex chromosomes (Baccetti et al, 2005;Godo et al, 2015;Wang et al, 2017) and chromosome 21 (Mahjoub et al, 2011;Vozdova et al, 2013;Hajlaoui et al, 2018) and a nonsignificant increase in the frequency of disomy for chromosome 18 (Machev et al, 2005;Douet-guilbert et al, 2005;Baccetti et al, 2005;Ogur et al, 2006;Chen et al, 2007;Kekesi et al, 2007;Wang et al, 2017;Olszewska et al, 2021).…”

“…The frequency of nullisomy for 13 chromosomes (3, 4, 6, 9, 11, 12, 16, 19-22, X, and Y) was significantly higher than that in normozoospermic men. Our results are consistent with those of previous studies in which significantly higher frequencies of sex chromosome nullisomy were observed (Ogur et al, 2006;Wang et al, 2017) and nullisomy 22 (Hajlaoui et al, 2018) and inconsistent with those of previous studies that reported significantly higher frequency of nullisomy 18 (Mahjoub et al, 2011;Vozdova et al, 2013;Hajlaoui et al, 2018). The aneuploidy rate was significantly higher than that in normozoospermic men, for all chromosomes, except for chromosomes 10, 17, and 18.…”

“…The analysis of numerical abnormalities for nontranslocated chromosomes has not been as extensive as that for chromosome 13 and 14. Mainly focusing on chromosomes 18, 21, 22, X, and Y (other chromosomes are rarely involved), researchers explored the possible interchromosomal effect (ICE) in male carriers of der (13;14) translocation (Hajlaoui et al, 2018;Wiland et al, 2020). The ICE was first proposed by Lejeune in 1963(Lejeune, 1963.…”

Aneuploidy in sperm of fertile men and patients with impaired fertility

“…Около 2 % мужчин с бесплодием являются носителями структурных хромосомных аномалий [53][54][55]. Наиболее частыми структурными вариантами являются робертсоновские транслокации (0,7-0,9 %) [53,55], реципрокные транслокации (0,6 %) и инверсии (0,2 %) [53].…”

“…Как правило, сбалансированные хромосомные аномалии у мужчин обнаруживают случайно, при цитогенетическом обследовании по поводу повторных выкидышей у супруги, рождения ребенка с хромосомными аномалиями или первичного бесплодия [55,56]. Носители этих хромосомных перестроек фенотипически нормальны (здоровы), но имеют высокий или повышенный риск нарушения фертильности из-за образования анеуплоидных гамет [55][56][57].…”