Exploring the DNA repair capacity of oocytes

Female fertility and offspring health are critically dependent on the maintenance of an adequate supply of high quality oocytes. Little is known about the DNA repair capacity of oocytes and the contribution of DNA repair to oocyte quality has not been investigated. We have shown that under conditions in which apoptosis is inhibited, lesions induced by radiotherapy are resolved in oocytes within 5 days. Remarkably, these oocytes produced healthy offspring, despite having sustained high levels of DNA damage. These exciting data strongly suggest that oocytes are in fact capable of efficient DNA repair and that DNA repair is an important mechanism for ensuring female fertility as well as the transmission of high quality genetic material to subsequent generations. Our lab is now characterizing the DNA repair response of primordial follicle oocytes, and determining if DNA repair can restore oocyte quality following DNA damage. We are also investigating the possibility that oocytes exhibit altered DNA repair responses with increasing age in humans and mice. Understanding the repair capacity of oocytes has important implications for the 1 in 5 Australian women who delay child bearing until later in life (>35 yr) when oocyte quality is greatly reduced, for understanding the origin of genetic disorders, and for the design of new therapies to inhibit oocyte death and preserve fertility during anti-cancer treatments. We use a variety of techniques, including qRT-PCR, Western blotting, stereology, immunofluorescence, in situ hybridisation, 3D confocal imaging and ELISA. We also have expertise in the design of long term fertility trials in mice, and the analyses of offspring health.