Biophysical studies of metabolic control in mouse oocytes and embryos

While a great deal is known about pathways and enzymology of carbohydrate metabolism, it is still poorly understood how metabolic fluxes are modulated during development and in response to environmental factors, or degraded in disease. Mounting evidence suggests that defects in metabolism may cause chromosome segregation errors in eggs and embryos, leading to age related infertility in women, but the possible underlying mechanisms remain unclear. We are developing and testing a coarse-grained biophysical model of enzyme engagement of electron carriers, with the goal of extracting metabolic fluxes from fluorescence lifetime imaging microscopy measurements. We are attempting to construct a theory of the control of mitochondrial respiration and cytoplasmic fermentation in mouse oocytes and embryos by using this approach in conjunction with metabolic manipulations. Our preliminary results argue that the fluxes through these pathways can be redirected in response to perturbations, but this is accompanied by large changes in cell biological features, including disassembly of the spindle, which we speculate might underlie the connection between metabolic defects and chromosome segregation errors.