Heterogoneic cell division provides a molecular explanation for the origin of gestational trophoblastic diseases in bovine and human

01 November 2019 → 31 October 2023
Research Foundation - Flanders (FWO)
Research disciplines
  • Agricultural and food sciences
    • Veterinary genetics
    • Veterinary reproduction and obstetrics
trophoblastic diseases
Project description

Early embryogenesis is burdened by chromosome abnormalities. Bovine mimics human early embryonic development and hence, is a good model to study chromosomal instability. During our studies, we discovered that cleavage stage embryos can contain both androgenetic (paternal only) and gynogenetic (maternal only) haploid cell lines as well as normal diploid and triploid cells. Those embryos must result from zygotes segregating entire parental genomes into distinct blastomeres. We coined this phenomenon heterogoneic cell division. Since complete hydatidiform moles are androgenetic, we hypothesize that those cell lines sometimes prevail during development and can cause molar pregnancies. Similarly, ovarian teratomas are gynogenetic. If placental teratomas are gynogenetic too, we believe that these are developing from gynogenetic cell lines in mixoploid embryos. We will test those hypotheses in both human and cattle by providing direct proof of heterogoneic cell division, by documenting the incidence of mixoploidy and chimaerism in bovine and human in vitro embryos, by collecting and dissecting molar and teratoma tissue and by monitoring the fate of mixoploid embryos in vivo. The transcriptional profiles of developing androgenetic and gynogenetic cells will be mapped. Overall, this study will provide insight into the developmental fate of haploid and triploid cells and is likely to provide a novel conceptual basis for the origin of trophoblastic disorders.