Meiotic Heterogeneity of Trivalent Structure and Interchromosomal Effect in Blastocysts With Robertsonian Translocations

BackgroundRobertsonian translocations are common structural rearrangements and confer an increased genetic reproductive risk due to the formation of trivalent structure during meiosis. Studies on trivalent structure show meiotic heterogeneity between different translocation carriers, although the factors causing heterogeneity have not been well elaborated in blastocysts. It is also not yet known whether interchromosomal effect (ICE) phenomenon occurs in comparison with suitable non-translocation control patients. Herein, we aimed to evaluate the factors that cause meiotic heterogeneity of trivalent structure and the ICE phenomenon.MethodsWe designed a retrospective study, comprising 217 Robertsonian translocation carriers and 134 patients with the risk of transmitting monogenic inherited disorders (RTMIDs) that underwent preimplantation genetic testing (PGT). Data was collected between March 2014 and December 2019. The segregation products of trivalent structure were analyzed based on the carrier’s gender, age and translocation type. In addition, to analyze ICE phenomenon, aneuploidy abnormalities of non-translocation chromosomes from Robertsonian translocation carriers were compared with those from patients with RTMIDs.ResultsWe found that the percentage of male carriers with alternate segregation pattern was significantly higher [P < 0.001, odds ratio (OR) = 2.95] than that in female carriers, while the percentage of adjacent segregation pattern was lower (P < 0.001, OR = 0.33). By contrast, no difference was observed between young and older carriers when performing stratified analysis by age. Furthermore, segregation pattern was associated with the D;G chromosomes involved in Robertsonian translocation: the rate of alternate segregation pattern in Rob(13;14) carriers was significantly higher (P = 0.010, OR = 1.74) than that in Rob(14;21) carriers, whereas the rate of adjacent segregation pattern was lower (P = 0.032, OR = 0.63). Moreover, the results revealed that the trivalent structure could significantly increase the frequencies of chromosome aneuploidies 1.30 times in Robertsonian translocation carriers compared with patients with RTMIDs (P = 0.026), especially for the male and young subgroups (P = 0.030, OR = 1.35 and P = 0.012, OR = 1.40), while the mosaic aneuploidy abnormalities presented no statistical difference.ConclusionsOur study demonstrated that meiotic segregation heterogeneity of trivalent structure is associated with the carrier’s gender and translocation type, and it is independent of carrier’s age. ICE phenomenon exists during meiosis and then increases the frequencies of additional chromosome abnormalities.

The Interchromosomal Effect: Different Meanings for Different Organisms

The term interchromosomal effect was originally used to describe a change in the distribution of exchange in the presence of an inversion. First characterized in the 1920s by early Drosophila researchers, it has been observed in multiple organisms. Nearly half a century later, the term began to appear in the human genetics literature to describe the hypothesis that parental chromosome differences, such as translocations or inversions, may increase the frequency of meiotic chromosome nondisjunction. Although it remains unclear if chromosome aberrations truly affect the segregation of structurally normal chromosomes in humans, the use of the term interchromosomal effect in this context persists. This article explores the history of the use of the term interchromosomal effect and discusses how chromosomes with structural aberrations are segregated during meiosis.

Meiotic nonhomologous coorientation in man

Концепция мейотической коориентаци негомологичных хромосом (МКНХ) как модели мейоза, экспериментально подтвержденная на Drosophila, была предложена в 1971 г. для объяснения интерхромосомного эффекта у человека, но с тех пор не получила достаточных доказательств. Представленные в настоящей статье данные «неканонического» поведения половых хромосом в определенных ситуациях являются основанием для признания существования этого явления в сперматогенезе человека. The concept of meiotic co-orientation of non-homologous chromosomes as a model of meiosis, experimentally confirmed in Drosophila, was proposed in 1971 to explain the interchromosomal effect in humans, but has not received sufficient evidence since. The data of the “non-canonical” behavior of sex chromosomes presented in this article are the basis for recognizing the existence of this phenomenon in human spermatogenesis.