On 26 November at 15 Olga Tšuiko will defend her doctoral thesis „Unravelling chromosomal instability in mammalian preimplantation embryos using single-cell genomics“.
Professor Andres Salumets (PhD (bioloogia)), Institute of Biomedicine and Translational Medicine ja Institute of Clinical Medicine, University of Tartu
Professor Joris Robert Vermeesch (PhD), Laboratory for Cytogenetics and Genome Research / Center for Human Genetics / KU Leuven, Belgia
Professor Ants Kurg (PhD (molekulaarbioloogia)), Institute of Molecular and Cell Biology, University of Tartu
Professor Joyce Harper (PhD), Department of Reproductive Health, Institute for Women’s Health, University College London, UK.
Fertility issues have become a plague of modern society, as one in six couples will encounter problems to achieve clinical pregnancy. Nowadays, natural conception is often taken for granted, leading to an increased number of couples that turn to assisted reproduction to help conceive and ultimately give birth to a healthy baby. In vitro fertilization (IVF) and embryo transfer is the most commonly performed procedure in ART. However, the uprising era of single-cell research has highlighted the alarming fact that human IVF embryos have high prevalence of chromosomal instability (CIN), which represents one of the most serious challenges in IVF. At the same time, the use of in vitro fertilization (IVF) treatment provides a unique opportunity to study the fundamentals of preimplantation human development, from fertilization to blastocyst stage of development. At the same time, embryo-related research is ethically one of the most complex areas of reproductive science that greatly relies on the use of appropriate animal models. By using novel single-cell genomics approaches, the current thesis has demonstrated that the nature and frequency of genomic abnormalities in in vitro cleavage-stage embryos is highly conserved between cattle and human. Additionally, heterogoneic cell division was discovered, by which the zygote segregates entire parental genomes into separate blastomere lineages, giving rise to mixoploidy and chimaerism, although the frequency of this phenomenon and the fate of mixoploid embryos remain to be investigated. By using the established bovine model it was demonstrated that chromosomal abnormalities are also present in naturally conceived embryos, but in vitro procedures exacerbate CIN in early embryos, compromising their survival rate. If this is the same for human this should encourage scientific and medical communities not only to refine and improve in vitro culture conditions, but also raise awareness among men and women of reproductive age. To tackle the issues of embryonic aneuploidy, embryo chromosome screening is performed, by analysing either day 3 or day 5 biopsy. Recently, the use of blastocoel fluid (BF) biopsy was proposed, but the data presented here shows that BF-DNA is not suitable for diagnostic purposes, and day 5 biopsy remains the safest option with the most reliable results.