Diploid/triploid mixoploidy: A consequence of asymmetric zygotic segregation of parental genomes

Abstract

Triploidy is the presence of an extra haploid set of chromosomes and can exist in complete or mosaic form. The extra haploid set of chromosomes in triploid cells can be of maternal or paternal origin. Diploid/triploid mixoploidy is a unique form of triploid mosaicism that requires the aberrant segregation of entire parental genomes into distinct blastomere lineages (heterogoneic cell division) at the earliest zygotic divisions. Here we report on eight cases of diploid/triploid mixoploidy from our institution and conduct a comprehensive review of the literature. The parental origin of the extra set of chromosomes was determined in two cases; and, based on phenotypic evidence we propose the parental origin in the other cases. One case with complex mixoploidy appears to have a digynic origin in addition to the involvement of two different sperm. Of our eight cases, only one resulted in the birth of a live healthy child. The other pregnancies ended in miscarriage, elective termination of pregnancy, intrauterine fetal demise or neonatal death. A review of the literature and the results of our cases show that a preponderance of recognized cases of diploid/triploid mixoploidy has a digynic origin. K E Y W O R D S 2n/3n, diploid/triploid, heterogoneic, mixoploid, mosaic triploid, triploid phenotype

Genome‐wide abnormalities in embryos: Origins and clinical consequences

“…These differences in triploid phenotypes likely reflect imprinting bias during prenatal development. As reviewed, 49 there also seems to be a variable ratio of digynic:diandric triploidy at different gestational age, with more digynic triploids surviving into the third trimester. This is likely due to the negative pronounced effect of diandry on placenta development and function, which might also potentially explain why diandric triploidy is associated with higher risk of maternal pregnancy complications 46 .…”

A Disorder of Sex Development in a Holstein–Friesian Heifer with a Rare Mosaicism (60,XX/90,XXY): A Genetic, Anatomical, and Histological Study

“…We suggest that the following events were responsible for this abnormality: (i) lack of extrusion of the second polar body, (ii) DNA replication and syngamy of male and female pronuclei, and (iii) postzygotic mitotic division accompanied by a random segregation of the nonreplicated unextruded second polar body, leading to the formation of the diploid and triploid blastomeres (Figure 6). This mechanism can be classified as asymmetric zygotic segregation of parental genomes [12] or heterogoneic cell division [18].…”

“…Animals 2021, 11, x 9 of 11 diploid and triploid blastomeres (Figure 6). This mechanism can be classified as asymmetric zygotic segregation of parental genomes [12] or heterogoneic cell division [18]. Several cases of diploid/triploid mixoploidy have been described in domestic mammals, specifically in cattle, cats, horses, and mink (Table 2).…”

“…To date, several such cases have been reported in domestic animals, including cattle [6][7][8], cats [9,10], and horses [11]. In humans, over eighty such patients have been diagnosed [12]. Interestingly, disorders of sex development have been observed in patients with 46,XX/69,XXY mixoploidy.…”

“…Mixoploidies (2n/3n) can occur in a form of mosaicism (where cell lines originate from a single zygote) or chimerism (where the lines are derived from different zygotes), and the additional genome can have a parental or maternal origin. Mixoploidy can be caused by: (a) delayed extrusion of the second polar body, followed by aberrant segregation of the entire parental genome into blastomeres during early embryonic mitoses; (b) fertilization by two sperms, followed by the fusion of one male pronucleus with the female pronucleus in a zygote and delayed fusion of the second male pronucleus with diploid nucleus of a daughter blastomere; or (c) the fusion of diploid and triploid embryos [12]. It is worth mentioning that cytogenetic analysis of mixoploid human patients, on the basis of in vitro cultured leukocytes, has usually revealed a normal diploid karyotype or a very low proportion of triploid metaphase spreads.…”