Chromosomal segregation in sperm of Robertsonian translocation carriers

Abstract

Purpose To study meiotic segregation patterns of Robertsonian translocations in sperm of male carriers and to assess the frequencies of unbalanced sperm formation. Methods FISH with combination of probes to detect all the variants of meiotic segregation was performed on decondensed sperm nuclei of 5 carriers of der(13;14), 3 carriers of der(14;21) and one carrier of a rare der(13;21) translocation. Results The frequency of sperm with alternate segregation and normal/balanced chromosomal complement ranged from 68 % to 94.4 % (mean 79.2±8.4). Adjacent segregation was detected in 17.9±7.3 % of sperm (from 5.6 % to 29 %). No significant differences in frequencies of gametes with nullisomies and disomies of chromosomes involved in translocations were observed. The mean frequency of 3:0 segregation products was 2.5±1.4 %. Conclusions All analyzed patients showed homogenous segregation pattern with clear predominance of alternate segregation resulting in normal/balanced sperm production. Still, from 5.8-32 % (mean 20.4±8.3 %) of sperm was unbalanced, which is the evidence of the increased risk of unbalanced offspring in carriers of Robertsonian translocations. Our results highlight the importance of genetic counseling of Robertsonian translocation carriers prior to ICSI or IVF.

Aneuploidy in spermatids of Robertsonian (Rb) chromosome heterozygous mice

“…In human male carriers of Rb translocations, alternate segregation has been described as being the most prevalent. Normal or balanced spermatozoa are present between about 77 and 93 %, while aneuploid spermatozoa, which result from adjacent segregation, has been reported as to be present between about 7 and 23 % (Anton et al 2004 ; Ogur et al 2006 ; Bernicot et al 2012 ; Pylyp et al 2013 ).…”

Altered segregation pattern and numerical chromosome abnormalities interrelate in spermatozoa from Robertsonian translocation carriers

“…Among them, 66 cases correspond to a t(13;14) reorganization (Anton et al, 2004;Brugnon et al, 2010;Chen et al, 2007;Escudero et al, 2000;Ferfouri et al, 2011;Frydman et al, 2001;Mahjoub et al, 2011;Morel et al, 2001;Nishikawa et al, 2007;Ogawa et al, 2000;Ogur et al, 2006;Pylyp et al, 2013;Roux et al, 2005) and 22 cases to a t(14;21) reorganization (Anton et al, 2010;Brugnon et al, 2010;Ferfouri et al, 2011;Honda et al, 2000;Nishikawa et al, 2007;Pylyp et al, 2013;Rousseaux et al, 1995). The remaining studies involve other rare combinations of acrocentric chromosomes (Acar et al, 2002;Anahory et al, 2005;Anton et al, 2010;Bernicot et al, 2012;Brugnon et al, 2010;Chen et al, 2007;Cinar et al, 2011;Ferfouri et al, 2011;Moradkhani et al, 2006;Nishikawa et al, 2007;Pylyp et al, 2013;Rogenhofer et al, 2012). As reviewed by Anton et al (2010), the compiled data indicate that Robertsonian translocation carriers display a similar distribution of segregation products, irrespective of the chromosomes involved, with the main segregation outcome being alternate (84.5% ± 6.3), followed by adjacent (14.6% ± 5.8) segregation, and the rare occurrence of 3:0 disjunction (0.6% ± 0.7).…”

The Importance of Cytogenetics and Associated Molecular Techniques in the Management of Patients Carrying Robertsonian Translocation and Their Pregnancy Outcome by Intracytoplasmic Sperm Injection

“…In general, carriers of Robertsonian translocations have a normal phenotype. However, they may have spermatogenesis alterations expressed by oligozoospermia or azoospermia, and they may be affected by reproductive failure owing to imbalances in chromosome meiotic segregation [8].…”