Figure 1
Proposed origin of FGSC from residual oogonia in the neonatal mouse ovary. During embryogenesis, PGC colonise the genital ridges at 10-11 d.p.c., transforming into (a) oogonia in the developing ovary, or (b) gonocytes in the developing testis. Both phenotypes undergo clonal expansion within syncytia until ~13.5 d.p.c., when proliferation ceases concurrently with downregulation of c-kit expression [121]. In (a), a minority of oogonia within germline cysts enter meiosis, while the majority arrest and eventually undergo apoptosis [33]. By 15.5 d.p.c., c-kit expression is undetectable in oogonia, indicating universal growth arrest [121, 123]. A proportion of oogonia persist in germline cysts after birth [109], comprising 10% of germ cells at day 7 postnatal [33]. The postnatal survival period of germline cysts is unknown. It is hypothesised that the residual oogonia occupy postmitotic and premeiotic stages of the cell cycle up to preleptotene, denoted here by an oogonium with condensed chromatin peripheral to the nuclear membrane. The preleptotene stage was described previously as a control point for entry into meiosis and G1 arrest [147], and also for relapse into mitosis [149, 150]. (In S. cerevisiae, reversion to mitosis has been demonstrated during meiotic differentiation, even after premeiotic DNA synthesis [151]). Therefore, postmitotic oogonia isolated from neonatal ovaries may resume division under conditions that stimulate SSC to proliferate as gonocytes [114, 148], while the oogonial phenotype and capacity for in vivo folliculogenesis [115] are maintained. This is the proposed origin of reported FGSC lines [10]. Similarly, residual oogonia may constitute the oocyte-producing component of cultures obtained by Pacchiarotti et al. [11] using SSC-based conditions [63]. In (b), gonocytes arrest in G1 as prospermatogonia (large interphase nucleus) at 13.5 d.p.c., resume mitosis at day 3 postnatal, and enter meiosis at day 7 postnatal. Absence of c-kit expression is depicted as a diagnostic feature of postmitotic oogonia and prospermatogonia [121, 123], which is shared by FGSC [10] and SSC [114] lines.