The aim of our research is to investigate chromosomal Instability in oocytes and embryos.

Maternal aging and meiosis
In women, advanced age predisposes to chromosome segregation errors during meiosis, which in turn leads to aneuploidy (incorrect number of chromosomes) in oocytes and after fertilization in developing embryos. Aneuploidy of meiotic origin is one of the major contributors of early miscarriage and congenital disorders such as Down’s syndrome in human embryos. We have recently showed that oocytes from aged female horses show a similarly high incidence of segregation errors during meiosis to human oocytes, making the horse a novel and attractive model to study maternal aging effects on meiosis.

This project aims to understand how, in oocytes from aged females, defects at the interface between chromosomes and the cytoskeletal machinery, lead to aneuploidy.

Techniques
Recovery of cumulus-oocytes complexes from slaughterhouse ovaries, in vitro maturation of oocytes, oocyte fixation, Immunofluorescence staining, confocal imaging and 3D imaging analysis

Chromosomal instability in embryos
Worldwide, over 6 million children have been conceived using in vitro fertilization (IVF) or
intracytoplasmic sperm injection (ICSI) and, nowadays, these techniques accounts for 2‐7% of all children born in Europe. Studies on human IVF embryos have revealed a surprisingly high level of chromosomal instability (CIN), with 70–90% of cleavage‐stage embryos containing at least one aneuploid cell (i.e. with an abnormal number of chromosomes). Recent evidence in large animal models has indicated that in‐vitro production markedly increases the likelihood of CIN in early embryos, however the mechanisms contributing to or preventing CIN in embryos are not understood.

This project aims to investigate the mechanisms of zygotic chromosome mis‐segregation in IVF embryos. Since, for ethical reasons, experimental studies are not feasible on human embryos, in our lab we investigate zygotic spindle assembly in large animal embryos which like human (but unlike mouse) embryos inherit the centrosome paternally.

Techniques
In-vitro maturation of oocytes, In vitro fertilization, embryo culture, treatments of zygotes with inhibitors, immunofluorescence, plasmids cloning, mRNA synthesis, live imaging, confocal microscopy.

The Group
The Stout Group is an enthusiastic research group that is currently composed of 4 PhD students, 2 postdocs, 2 technicians and a variable number of undergraduate students. The lab is well equipped and the location within the university campus provides ample opportunities for collaboration. In addition we have a number of ongoing collaborations with the Hubrecht Institute (Netherlands) and the Ellenberg group from the European Molecular Biology Laboratory (EMBL) in Heidelberg (Germany).

Interested?
We are currently looking for highly motivated undergraduate students to start a research projects on chromosome segregation in oocytes and embryos. Input of the candidate is appreciated. If you are interested please send your CV and motivation letter to Dr. Marta de Ruijter‐Villani (m.villani@uu.nl).

Location
Utrecht University, Veterinary Medicine
Department of Equine Sciences, Section Reproduction and Obstetrics
Yalelaan 104
3584 CM Utrecht
Website: www.uu.nl/medewerkers/MdeRuijterVillani/Onderzoek