Influence of p53 and genetic background on prenatal oogenesis and oocyte attrition in mice

Abstract

Meiotic progression, and the number of oocytes surviving to birth, determine the ovarian reserve, yet the control of prenatal oogenesis is poorly understood. We investigated the effects of genetic background and p53 upon oogenesis in mice. Fetal and neonatal ovaries were analysed in B6CBf1 and B6CBf2 mice from 15.5 to 21 days post-coitum (dpc) and p53 (a tumour suppressor gene) knockout, heterozygous and wild-type mice from 15.5 to 16 dpc. Oocytes in meiotic prophase I (MPI) were identified by labelling synaptonemal complex protein 3, and the specific stage of MPI was classified by the appearance of axial elements. Apoptosis and DNA breaks were assessed by cleaved poly-(ADP-ribose) polymerase (PARP-1) and terminal deoxynucleotidyltransferase-mediated dUTP nick-end labelling (TUNEL), respectively. The leptotene, zygotene and pachytene stages were earlier in f1 than f2 generations with significant differences at all stages (P< or =0.002). The p53(-/-) oocyte populations and those with the presence of p53 gene differed significantly in terms of: (i) the proportion of oocytes reaching specific stages of MPI on 15.5 and 16 dpc and (ii) the proportion of oocytes having observed abnormalities in synaptonemal complexes (P < 0.001). The absence of p53 resulted in faster progression of oocytes and more with compressed and abnormal axial elements. We observed significant differences between p53(-/-), p53(+/-) and p53(+/+) mice in terms of cleaved PARP-1 staining and TUNEL. Genotype has an important impact on prenatal meiosis and oocyte apoptosis. p53 affects the speed of oocyte development and may influence the oocyte selection through apoptosis during MPI.