PhD Defense: Aneuploidy in horse oocytes and embryos; how late is too late?

Summary

Advanced mare age is associated with reduced fertility, primarily because of a higher incidence of early pregnancy loss (EPL). Moreover, aberrations of embryonic chromosome number (aneuploidy) appear to be the primary contributor to this age-related increase in EPL. The aim of this thesis was to examine how advancing mare age predisposes to aneuploidy in horse oocytes or embryos. In particular, we investigated the potential contributions to aneuploidy of reduced cohesion between sister-chromatids and less stringent regulation of chromosome alignment during the meiotic divisions. We also compared the incidence of micronuclei, a proxy for mitotically-derived aneuploidy, in in vitro produced (IVP) versus in vivo derived embryos. Finally, we looked for correlations between light microscopic characteristics of IVP embryos, the incidence of nuclear abnormalities and the likelihood of pregnancy (or EPL) after transfer. We showed that advanced mare age predisposes to chromosome misalignment and aneuploidy in in vitro matured oocytes, with probable contributions from both weakened inter-chromosomal cohesion and defective function of proteins regulating the timing of chromosome segregation. In addition, IVP horse embryos contained more micronuclei, indicating a high incidence of mitosis-derived aneuploidy. On the other hand, the only characteristics of IVP horse embryos that correlated with pregnancy success were the speed of development and the developmental stage at which an embryo was transferred to a recipient mare. The increased incidence of oocyte and early embryonic aneuploidy presumably explains why advancing mare age is associated with a higher risk of EPL.