Figure 16

Working model of possible pathways for formation of primary follicles in adult human ovaries (updated from Ref. [32]). 1) Ovarian tunica albuginea (ta) stem cells (green color) differentiate into the CK+ fibroblasts (red color) and by mesenchymal-epithelial transition give rise to the SE cells directly covering the ovarian cortex (arched arrow). 2) Closing of TA flaps (see Fig. 1) results in the formation of epithelial cords/channels in the upper ovarian cortex (see Fig. 3). Fragmented epithelial cords give rise to the epithelial nests, which resemble primitive granulosa cells [22] and descend into the lower ovarian cortex. 4) Depending on certain in situ (stromal) 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 putative germ cells may 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 (yellow 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 [22,25], 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.