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

Abstract

Background: Robertsonian 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.

Methods: We 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.

Results: We 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.

Conclusions: Our 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.

Keywords: ICE; Robertsonian translocation; meiotic heterogeneity; segregation patterns; trivalent structure.

FIGURE 1

The distribution of segregation products in blastocysts among different translocation karyotypes. Legend: (A) represents the distribution of alternate segregation products; (B) represents the distribution of adjacent segregation products. Horizontal axis represents different translocation types, Rob(13;14)(q10;q10); Rob(13;15)(q10;q10); Rob(13;21)(q10;q10); Rob (13;22)(q10;q10); Rob(14;15)(q10;q10); Rob(14;21)(q10;q10); Rob(14;22)(q10;q10); Rob(15;21)(q10;q10); Rob(15;22)(q10;q10); and Rob (21;22)(q10;q10), respectively.

FIGURE 2

The comparison of meiotic segregation products of non-translocation chromosomes in blastocysts between Robertsonian translocation carriers and patients with RTMIDs. Legend: The trivalent structure could significantly increase the frequencies of chromosome aneuploidy 1.30 times in Robertsonian translocation carriers compared with patients with RTMIDs (P = 0.026), especially for the male and young carriers group (P = 0.030, OR = 1.35 and P = 0.012, and OR = 1.40). By contrast, the mosaic chromosome aneuploidy presented no statistical difference between the two groups. For elder carriers, no difference was observed between different subgroups.

FIGURE 3

The distribution of non-translocation chromosome abnormalities in blastocysts of Robertsonian translocation carriers and all chromosome abnormalities in blastocysts of patients with RTMIDs. Legend: Horizontal axis represents chromosome 1-XY, vertical axis represents the proportion of aneuploidy and mosaic aneuploidy abnormalities. For Robertsonian translocation carriers, 977 blastocysts were included, and for patients with RTMIDs, 875 blastocysts were included in this study. RTMIDs, risk of transmitting monogenic inherited disorders.