Mitochondria take centre stage: pathways to reduced oocyte quality and opportunities for curative strategies under maternal metabolic stress conditions.

Infertility is a major socio-economic problem affecting millions worldwide and is specifically linked to maternal obesity and other (diet induced) metabolic disorders. Understanding the mechanisms by which altered metabolism affect fertility is crucial for successful interventions. Mitochondria are the power house within the oocyte. Reduced somatic cell mitochondrial function occurs early in the pathogenesis of metabolic diseases. This is mainly due to the lipotoxic effects of elevated free fatty acid concentrations in blood. For the oocyte to be developmentally competent, the number and function of mitochondria should reach a certain threshold. There are several thousands of mitochondria in the mature oocyte derived from about 20 mitochondria in the germ cell. In addition to their bio-energetic roles, mitochondria are also sensors of stress. Oxidative stress and associated cellular damage elicit stress signalling between the mitochondria and the nucleus to start a protective machinery. The effects of metabolic stress on mitochondrial replication and stress responses during oocyte growth and subsequent embryo development are not known. In this project we will use in vitro and in vivo animal models to study mitochondrial functions and stress responses under maternal metabolic stress conditions in growing oocytes. Defect-based protective and rescue interventions will also be tested to investigate opportunities for curative interventions.

Keywords:MITOCHONDRIAL RESEARCH

Disciplines:Animal biology, Veterinary medicine, Other veterinary sciences, Other agricultural, veterinary and food sciences

Project type:Collaboration project