Multifaceted programmed cell death in the mammalian fetal ovary

From previous and more recent works reviewed in the present paper, it appears that mammalian fetal oocytes face several challenges to survive throughout the stages of meiotic prophase I up to the block at the diplotene/dictyate stage and the primordial follicle assembly. Depending on the period of development and experimental conditions, these oocytes can undergo different forms of programmed cell death (PCD) and cross-talking pathways. We hypothesize that they require the continuous support of growth factors to accomplish the activities required to overcome PCD during prophase I. An extraordinary level of DNA double strand break (DSB) tolerance characterizes oocytes during the first stages of meiotic prophase I. However, the activation of a p63/p53-and PCNA-dependent DNA damage checkpoint, plays a major role in eliminating defective oocytes when they reach the diplotene stage. Before oocytes are enclosed into a primordial follicle, the shortness of nutrients/growth factors might activate protective autophagy but this can turn into their death if starvation is prolonged. Actually, clarifying the relationships among growth factor signalling (mainly AKT cascade), apoptotic and autophagic proteins that seem to coexist in fetal oocytes, could be the key to understanding PCD in these cells.