Understanding how faulty cell division arrises will create strategies to preserve developmental ability of eggs 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 fertilisation in developing embryos. Embryo aneuploidy of meiotic origin is one of the major contributors of early miscarriage and congenital disorders such as Down’s syndrome. We have recently shown that oocytes from aged mares show a similarly high incidence of segregation errors as human oocytes, making the horse a novel and attractive model to study maternal aging effects on meiosis. Our aim is to understand how, in oocytes from aged females, defects at the interface between chromosomes and the cytoskeletal machinery, lead to aneuploidy.
Chromosomal instability in IVF embryos
Worldwide, over 6 million children have been conceived using in vitro fertilisation (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.
Since, for ethical reasons, experimental studies are not feasible on human embryos, our aim is to investigate the mechanisms of spindle assembly and chromosome mis-segregation in IVF embryos using large animal models.