Marta de Ruijter-Villani research focuses on chromosomal instability in oocytes and embryos.

Maternal aging and meiosis

Oocytes (eggs) have to undergo two rounds of cell division (Meiosis I and Meiosis II) before being able to be fertilized by the spermatozoon (sperm cell) and further develop into an embryo. During oocyte meiosis the chromosomes are segregated into the mature oocytes and the polar bodies, so that the mature oocyte possesses only one pair of chromosomes (haploid), which, after fusion with the paternal haploid set of chromosomes introduced by the spermatozoon during fertilization, contributes to form the diploid zygote (containing two sets of chromosomes, one of paternal and one of maternal origin).

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. Oocytes from aged female horses show an incidence of segregation errors during meiosis very similar to human oocytes, making of the horse a novel and attractive model to study maternal aging and meiosis.

Our aim is to understand how, in aged females oocytes, defects at the interface between chromosomes and the cytoskeletal machinery, lead to aneuploidy in eggs.

Chromosomal instability in embryos

In vitro fertilization (IVF and embryo culture) have become a routine and essential component of human clinical reproduction, however these methods still suffer from a relatively low efficiency per treatment cycle. Approximately two thirds of IVF embryos fail to implant, and of those that do implant, the incidence of pregnancy loss is very high (17-21%). It is increasingly clear that implantation failure and pregnancy loss after IVF are primarily a factor of chromosomal abnormalities in the embryo (abnormal number or structure of chromosomes); these abnormalities impair the ability of the embryonic cells (blastomeres) to survive and proliferate, leading to developmental arrest and implantation failure, pregnancy loss and DNA mutations in children. 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). Similarly to human embryos, large mammals (equine and bovine) embryos produced in vitro are also extremely predisposed to CIN.

Our aim is to understand the mechanisms that induce chromosome instability in IVF large animal (bovine and equine) embryos and to study the consequences of CIN on early development. To this end we have developed molecular tools to target key players in the mechanisms of aneuploidy generation and establish large animal embryos as a standard cell biological model system.

Bovine zygote forming two separate spindles around the maternally and paternally inherited chromosomes

My group is currently looking for highly motivated undergraduate students to start a research projects on chromosome segregation in oocytes and embryos. If you are interested please send your CV and motivation letter to Dr. Marta de Ruijter-Villani (m.villani@uu.nl).