Towards understanding human ovarian ageing

When a woman ages, her oocyte quality declines, which is part of a phenomenon known as ovarian ageing. This results in several fertility problems, such as a lower chance of conceiving and an increased number of chromosomal abnormalities in clinically recognized pregnancies. This thesis explores the biological mechanisms that drive ovarian ageing.
In this thesis it is shown that there is no difference in percentage of chromosomal abnormalities in single or recurrent pregnancy losses. Furthermore, several studies were performed on ovarian tissue, oocytes, and cumulus cells of women of different ages. Gene expression analysis of single oocytes showed that, with increasing female age, the expression of pro-longevity pathways decreases, while the expression of anti-longevity pathways increases. Immunofluorescence microscopy, metabolomics and lipidomics analyses demonstrated that oocytes of women of advanced maternal age display increased oxidative damage and mitochondrial dysfunction, hampering their energy supply. At the same time alternative energy sources, like glycolysis and ATP from surrounding cumulus cells, were demonstrated to increase and thus seemed to act as backup energy sources for the older oocyte.
Future research on therapeutics that target this oxidative damage or that increase mitochondrial function may help to prevent the effects of ovarian ageing.