Figure 5

Comparison of human oogenesis in vivo and in vitro a) A working model of possible pathways for oogenesis and formation of primary follicles in adult human ovaries in vivo (adjusted from Ref. [6]). (1) Ovarian tunica albuginea (ta) stem cells (green color) first differentiate into the CK+ fibroblasts (blue color) and by mesenchymal-epithelial transition give rise to the SE cells directly covering the ovarian cortex (arched arrow). (2) Closing of TA results in the formation of epithelial cords in the upper ovarian cortex. (3) Fragmented epithelial cords give rise to the epithelial nests, which resemble primitive granulosa cells and descend into the lower ovarian cortex. (4) Depending on certain in situ (stromal and neuronal) and systemic (hormonal) influences, the TA progenitors differentiate into the SE cells covering TA, which may, by asymmetric division, give rise to the ZP+ germ cells. (5) These primitive germ cells symmetrically divide, descend into the ovarian cortex, and associate with adjacent cortical vessels (6). Intravascular transport (7) is associated with a substantial increase of germ cell size and with development of ZP+ anchors (green lines), which may serve to slow down the transport speed and signal the epithelial nests to associate with a particular vascular segment. 8) The intravascular germ cells differentiating into the oocytes are picked up by epithelial nests associated with the proper cortical vessels. Such oocyte-nest complexes show an "octopus-like" (9) formations during the early stage of assembly, and a formation of the Balbiani body during the intermediate stage (light blue body, 10). The Balbiani body persists in resting primary follicles (11), but diminishes upon the growth promoting signals, including Thy-1 dp signaling derived from the follicle-accompanying vessels (12, dashed line). An alternative pathway for the germ cell origin from TA precursors (4') consists of a constitution of cortical crypts formed by SE-like embryonal type cells, possibly originating from, but not necessarily connected with the deep SE invaginations, as evidenced from serial sections. The "alternative" pathway of germ cell origin may supply the oocytes directly to the neighboring nests (dashed arched arrows) and, via vascular transport (dotted arched arrow), saturate distant nests to form the primary follicles. The oocytes not utilized for follicular renewal accumulate in medullary vessels and degenerate (bottom right) [6]. b) In vitro, the CK5+ oocyte precursors may differentiate into CK5- cells (see Fig 2g), enlarge and undergo germinal vesicle breakdown followed by first meiotic division with a release of the polar body (pb) and ZP surface expression (brown color, see Fig. 3e and 4h).