Interchromosomal effect in sperm of males with translocations: report of 6 cases and review of the literature

Abstract

Somatic chromosomal abnormalities are frequently found in infertile men, particularly in those with low sperm count and/or seeking intracytoplasmic sperm injection. These abnormalities mostly consist of numerical sex chromosome abnormalities and translocations (Robertsonian or reciprocal). In this study, we searched for the occurrence of non-disjunction of chromosomes not involved in translocations during meiosis, phenomenon called interchromosomal effect (ICE) and first described by Lejeune (1965). Ejaculate samples of two patients carrying a Robertsonian translocation and four a reciprocal translocation patients and four controls (men with a 46,XY karyotype and normal sperm parameters) were studied in dual FISH 7-9, dual FISH 13-21 and triple FISH X-Y-18. A statistically significant increase of disomy X, Y and XY (P = 0.009, P = 0.004, P < 0.001) was found in the Robertsonian der(13;14)(q10;q10) carrier but not in the der(14;21)(q10;q10) carrier compared with controls. Among reciprocal translocation carriers, a significant increase of disomy 21 (P = 0.033) was observed in a sole patient with a t(9;22)(q21;q11.2). The increase of meiotic non-disjunction for chromosome 21 and sex chromosomes is a recurrent event found in other studies. According to our results and published data, the ICE on some specific chromosomes is likely in men carrier of a translocation, although it cannot be excluded that the aneuploidy is related to the oligoasthenoteratozoospermia usually present in these men. Moreover, this phenomenon showed interindividual variations which cannot be predicted. The risk of aneuploidy in sperm of males used for ICSI need to be evaluated. It could be superadded to that of meiotic segregation of the translocation to give a more precise and personalized risk assessment of aneuploidy in the offspring of those men.

Analysis of meiotic segregation patterns and interchromosomal effects in sperm from six males with Robertsonian translocations

“…In addition, the rates of diploid were significantly higher in two t(13;14) carriers (P3 and P4) compared with controls. Similar results were made previously by other studies [15][16][17]. This mechanism of meiotic non-disjunction for sex chromosomes may be the results of a non-random association at prophase I between the trivalent and the sex chromosomes [22,23].…”

“…Some reports supported the possibility of ICE in Rob translocations [5,8,[14][15][16][17]26]. However, others demonstrated no evidence of this phenomenon [12,18,19].…”

“…In current study, the possibility of ICE was found in common and uncommon Rob translocations with poor sperm quality (P2, P3, P4 and P6). Reviewing the published data, Rob translocation carriers with an increased rate of aneuploidy always had the oligozoospermia or oligoasthenoteratozoo spermia [15][16][17]. Therefore, more cases should be investigated to confirm whether the increased aneuploidy frequency in Rob translocation carriers is truly the result of ICE or is associated with abnormal sperm.…”

“…Contradictory data have been reported on the analysis of spermatozoa. Several studies have found such an ICE in male carriers of Rob translocations [8,[14][15][16][17], but others did not [12,18,19].…”

Genomics revolution on andrology: genetic testing for male infertility

“…The risk of male's sperm aneuploidy used for intracytoplasmic sperm injection (ICSI) needs to be evaluated to prevent the further aneuploidy in the offspring of these men. Some studies [3,4] revealed that the infertile men with normal karyotypes possessed higher frequency of sperm aneuploidy, specifically the sex chromosomes. Male carriers of Robertsonian translocations are vulnerable for fertility problems as evident from 14 Robertsonian carriers [5].…”