Balancing between totipotency and differentiation in human embryos.

Student thesis: Doctoral Thesis

Abstract

Today, it has become clear that the information on critical factors of
human embryo development should result in the optimization of IVF
techniques. The unique properties of human embryonic blastomeres,
responsible for the ability of human embryos to recover after cell loss,
became a target of our investigation. In this context, we analyzed two
new markers - CAR and CCNE1 - and the WNT/ -catenin signaling in
human preimplantation embryos in vitro. CAR is a gene, encoding the
coxsackie and adenoviral receptor, which is induced in regenerating and
developing tissues. We described a soluble CAR marking undifferentiated
blastomeres and trophectoderm (TE) cells of hatching blastocysts and a
transmembrane CAR relating to epithelial-like cell types via its
association with tight junctions. Our further investigation was focused on
CCNE1 as link between the developmental potential and the unique cell
cycle characteristics. We reported ubiquitous presence of CCNE1 protein
from the cleavage stages until blastocyst expansion. CCNE1 also labeled
the third lineage within blastocysts’ inner cell mass (ICM), which has
never been described before. We associated CCNE1 with a visceral
endoderm-like phenotype and proved its critical role in human embryonic
cells during normal embryo development and hESC derivation. We also
performed WNT/ -catenin pathway loss- and gain-of-function studies
and showed relevance of the nuclear -catenin exclusively to cleavage
stages. The balanced -catenin activity was critical for the TE fate.
Similar to stabilized -catenin, WNT3 protein, showing TE-specific
expression in blastocysts, promoted trophoblast specification. The data
from this work have led to a better understanding of early human
embryogenesis, which is important for reproductive medicine.
Date of Award3 Sep 2015
Original languageEnglish
Awarding Institution
  • Vrije Universiteit Brussel
SupervisorHilde Van De Velde (Promotor), Mieke Geens (Promotor), Christiaan Van Schravendijk (Jury), Leo van Grunsven (Jury), Ileana Mateizel (Jury), Stéphane Viville (Jury) & Kelly Tilleman (Jury)

Keywords

  • human embryo
  • IVF
  • human embryonic blastomeres
  • PGD

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