DNA damage and apoptosis in fetal and ovarain reserve oocytes

The integrity of the nuclear DNA is constantly being challenged by environmental agents but also by several processes physiologically occurring within the cell such as free radical formation and DNA replication and recombination. It has been estimated that as many as 10.000 DNA lesions may occur each day in a metabolically active mammalian cell. The web of control mechanisms of the nuclear DNA damage has been called genome surveillance system. Various types of DNA damage may occur and are repaired by a variety of DNA repair systems, each of which is dedicated to a particular class of lesions. In humans, for examples 130 DNA repair genes have been reported (Wood et al. 2001). In general, the activation of DNA repair mechanisms awakes parallel cell death pathways leading to various types of apoptosis, if the DNA repair fails. In mammals, the oocyte genome is challenged by two unique processes such as the meiotic recombination of homologous chromosomes during the fetal life and a long post natal period of meiotic arrest (dictyate stage) preceding the completion of the meiotic divisions. Meiotic recombination imposes hundreds of DNA double strand breaks (DSBs) that are usually repaired by the oocyte at the end of the meiotic prophase I. The dictyate stage represents a period in which the DNA of the oocytes is subjected to a variety of potential damages whose effects can be highly detrimental for female fertility. In the present chapter, we have attempted to review what it is known about the capability of the fetal and ovarian reserve oocytes, mainly of the mouse, on which most of the studies in mammals have been performed, to repair DNA damages, namely DSBs, produced by meiotic recombination or by external agents, and the relationship between this process and the activation of cell death in such cells.