La génomique cellulaire unique pour démêler les aspects fondamentaux du développement préimplantatoire

 

Sophie Petropoulos

Centre hospitalier de l'Université de Montréal [CHUM]

 

Domaine : santé de la mère, des enfants et des adolescents

Programme Chercheurs-boursiers - Junior 1

Concours 2019-2020

The first week of embryo development is arguably the most critical window. During this time, the first lineages are being established, however, fundamental knowledge pertaining the mechanism(s) driving lineage segregation remain unknown.   Further, the environment can have a profound and lasting impact on the developmental trajectories and longer-term health outcomes of the offspring. Given the dynamic developmental events that occur during this period, environmental ‘insults' may affect not only the viability of the embryo and ability of the blastocyst to implant, but also the developmental trajectory of the lineages ultimately impacting the long-term health of the child. Subfertility affects 1 in 6 couples and despite advances in assisted reproductive medicine (ART), the current rate of success remains at ~25%.  Glucocorticoids (GCs) are used as an adjuvant therapy to improve success despite the lack of evidence supporting the effectiveness of this treatment.  Strong scientific evidence for the safety of adjuvant therapies and additives utilized to increase the success rate of IVF is lacking. We are now the first to provide scientific evidence that the embryo is susceptible to GC reprogramming.

My research group aims to 1)determine underlying mechanism(s) of lineage segregation and transcriptional changes observed, 2)determine the longer-term impact of preimplantation GC exposure on neuroectoderm specification, and 3)determine a novel animal model to study human preimplantation embryo development. This work will develop a landscape (methylome and small ncRNA) at a single-cell resolution during human preimplantation development and determine the functional role of small ncRNA in driving lineage segregation; shedding light into a currently unknown process in the human embryo.  Further, these studies will determine the programming potential of preimplantation GC exposure. Data from these studies will be of importance not only for attaining fundamental knowledge pertaining to early development but also for improving clinical outcome of ART and assessing embryo quality.