My main research interest is to investigate the molecular mechanism underlying human
oocyte aneuploidy. Aneuploidy arising through chromosome mis-segregation during meiosis is a major
cause of infertility and inherited birth defects. Aneuploid embryos account for at least 10% of human
pregnancies in young women. Today, parenthood occurs at older ages, and in women nearing the end of
their reproductive lifespan, the incidence may exceed 50%.
Proteins that contribute to oocyte
aneuploidy are therefore of central interest. Germinal Vesicle (GV) stage it is a very unknown stage,
in spite of being the longest phase of the meiosis in human oocyte. Thus, in the lab we aim to decipher
the architecture of chromosome at this stage as well as the proteins that accompany the chromosomes
during meiosis resumption from GV stage to the metaphase II oocyte, so called mature egg. One of the
recently described aneuploidy factor in the mice oocyte is CENP-V. CENP- V is involved in centromeric
cohesion, chromosome alignment and segregation in HeLa cells.
CENP-V depleted cells die within 2-3 days. A previous work in mice show that around 40%
of CENP-V deficient mice oocytes arrest at meiosis I and the 60% that proceed to metaphase II show high
level of aneuploidy. CENP-V support correct chromosome segregation through the interaction to spindle
microtubules. By contrast, preliminary experiments in human eggs show a huge difference in the localization
of CENP-V compared to mouse oocytes, raising the question of whether CENP-V has a different role in human
meiosis. This caveat suggests the need to translate the study of CENP-V to human eggs. The aim of the lab
is to investigate the role of CENP- V in aneuploidy and ageing in human female meiosis. The potential use
of CENP-V as a biomarker for IVF applications will be also explored.
However, understanding the basis for errors in human oocytes meiosis is hampered by limited
access to the cells and by the fact that meiotic prophase in mammals occurs during embryogenesis. To overcome
this limitation, in parallel to the human study, the role of CENP-V in the oocyte aneuploidy will be analyzed
in Caenorhabditis elegans. The nematode is a model system to study meiotic prophase in which most of the
molecular mechanisms are conserved to humans.
