Due to copyright issues, an electronic copy of the thesis must be ordered from the faculty. For the faculty to have time to process the order, the order must be received by the faculty at the latest 2 days before the public defence. Orders received later than 2 days before the defence will not be processed. After the public defence, please address any inquiries regarding the thesis to the candidate.
Trial Lecture – time and place
See Trial Lecture.
Adjudication committee
- First opponent: Professor of Developmental Biology Susana Chuva de Sousa, Leiden University Medical Center, The Netherlands
- Second opponent: Goup leader, Principal Investigator Sebastian Preissl, University of Freiburg, Germany
- Third member and chair of the evaluation committee: Professor Heidi Kiil Blomhoff, Faculty of Medicine, University of Oslo
Chair of the Defence
Professor emeritus Guttorm Haugen, University of Oslo
Principal Supervisor
Research Scientist Gareth Greggains, Oslo University Hospital
Summary
An estimated one out of eight couples will experience difficulties in trying to conceive. Despite the vast number of people affected globally, our understanding of the molecular mechanisms underlying infertility remains limited.
Epigenetic modifications are key regulators of gene transcription, and recent advances in highly sensitive epigenetic technologies have enabled the profiling of epigenetic modifications in scarce cell types. This have led to the discovery that correct establishment of the epigenetic landscape is required for normal oocyte and early embryo development, and that epigenetic aberrations may contribute to infertility in mammals.
This PhD thesis describes the role of an epigenetic histone modification, H3K4me3, in the acquisition of developmental competence in mouse and human oocytes and early embryos.
First, we describe the development of an optimized method of chromatin immunoprecipitation followed by sequencing, applicable to minimal input chromatin and single-cell analysis of histone modifications (picoChIP-seq). We reveal that broad H3K4me3 domains are fully established at an important time point during oocyte maturation, linking epigenetics to the acquisition of meiotic and developmental competence of the oocyte.
Next, we profile H3K4me3 in human oocytes and embryos, and discover that the H3K4me3 landscape in human oocytes is distinct from that found in other mammals studied. Finally, we observe that human embryos with defective development display aberrant H3K4me3 profiles, suggesting a link between aberrant H3K4me3 programming and early human embryo developmental failure.
Greater insight into human oocyte and embryo development, and the regulatory epigenetic mechanisms involved, is of critical importance for the study of basic human reproductive biology and may direct improvements in treatment for infertility.
Additional information
Contact the research support staff.