Chromosome segregation errors, Infertility, and assisted reproductive technologies

Even in young, healthy individuals, over half of fertilized eggs spontaneously abort.  Success rates decrease dramatically further with advancing maternal age, increasing maternal body mass index (BMI), and as a result of exposure to adverse substance.  Cytological analysis demonstrates that a significant fraction of spontaneously aborted embryos contain severe meiotic or mitotic errors in chromosome segregation, the precise cause of which remains unclear. It has repeatedly been proposed that the state of energy production, associated with cellular respiration, is a primary determinant of the dynamics and fidelity of cell division, though the validity of this hypothesis remains unclear.  We are investigating the possible connection between malfunctions in mitochondria and malfunctions in spindle function, and we are attempting to use our results to improve IVF success rates.

We study the development of oocytes and embryos from single cells to blastocyst, using two-photon and other non-linear microscope techniques that can determine the developmental status. We track developmental tracers such as the presence of polar bodies within the egg follicles or concentrations of endogenous metabolites, such as NADH or FAD with respect to metabolic perturbations such as changes in oxygen levels. 

This work is associated with LuminOva with the aim of developing imaging techniques for clinical applications.  


Project Members:

Tim Sanchez

Post-Postdoctoral Fellow