DNA damage and repair in human oocytes and embryos: a review

Abstract

The genome of all cells is protected at all times by mechanisms collectively known as DNA repair activity (DRA). Such activity is particularly important at the beginning of human life, i.e. at fertilization, immediately after and at the very onset of embryonic development. DRA in early development is, by definition, of maternal origin: the transcripts stored during maturation, need to control the integrity of chromatin, at least until the maternal/zygotic transition at the 4- to 8-cell stage in the human embryo. Tolerance towards DNA damage must be low during this critical stage of development. The majority of DNA damage is due to either apoptosis or reactive oxygen species (ROS). Apoptosis, abortive or not, is a common feature in human sperm, especially in oligoasthenospermic patients and FAS ligand has been reported on the surface of human spermatozoa. The susceptibility of human sperm to DNA damage is well documented, particularly the negative effect of ROS (Kodama et al., 1997; Lopes et al., 1998a, b) and DNA modifying agents (Zenzes et al., 1999; Badouard et al., 2007). DNA damage in sperm is one of the major causes of male infertility and is of much concern in relation to the paternal transmission of mutations and cancer (Zenzes, 2000; Aitken et al., 2003; Fernández-Gonzalez, 2008). It is now clear that DNA damaged spermatozoa are able to reach the fertilization site in vivo (Zenzes et al., 1999), fertilize oocytes and generate early embryos both in vivo and in vitro. The effect of ROS on human oocytes is not as easy to study or quantify. It is a common consensus that the maternal genome is relatively well protected while in the maturing follicle; however damage may occur during the long quiescent period before meiotic re-activation (Zenzes et al., 1998). In fact, during the final stages of follicular growth, the oocyte may be susceptible to damage by ROS. With regards to the embryo there is active protection against ROS in the surrounding environment i.e. in follicular and tubal fluid (El Mouatassim et al., 2000; Guerin et al., 2001). DNA repair activity in the zygote is mandatory in order to avoid mutation in the germ line (Derijck et al., 2008). In this review we focus on the expression of mRNAs that regulate DNA repair capacity in the human oocyte and the mechanisms that protect the embryo against de novo damage.