Figure 1.

DNA damage models and impact of DNA damage on oocytes. (A) Oocyte growth during follicle development. Oocytes undergo an extensive period of growth, while follicles develop from primordial to antral stages. Large antral-stage follicles contain fully-grown oocytes arrested at first meiotic prophase, identifiable by the presence of an intact germinal vesicle (GV). (B) Oocytes within primordial follicles, which sustain severe DNA damage trigger a TAp63-dependent pathway resulting in follicular apoptosis. (C) DNA damage sustained in vivo which does not trigger primordial follicle apoptosis persists throughout oocyte growth resulting in damaged fully-grown oocytes within antral-stage follicles. (D) The canonical model for studying the effects of DNA damage in fully-grown oocytes. Fully-grown oocytes with intact DNA are isolated from young female mice and subject to acute treatment with agents such as chemotherapy drugs to induce severe levels of damage. Note that the key differences between in vivo damage (C) and the in vitro experimental model (D) are, firstly, in vivo damage is much milder than in vitro-induced damage and, secondly, in vivo damage persists for weeks to months during oocyte growth vs. hours in the case of the in vitro model.