As a primordial follicle develops into a growing follicle, changes occur in the oocyte, in the follicle cells, and in the adjacent stroma. Initially, the oocyte enlarges, and the surrounding flattened follicle cells proliferate and become cuboidal. At this stage—that is, when the follicle cells become cuboidal— the follicle is identified as a primary follicle. As the oocyte grows, it secretes specific proteins that are assembled into an extracellular coat called the zona pellucida. It appears between the oocyte and the adjacent follicle cells (Fig. 23.4). The zonal pellucida in humans is composed of three classes of sulfated acidic zona pellucida (ZP) glycoproteins termed ZP-1 (80 to 120 kilodaltons), ZP-2 (73 kilodaltons), and ZP-3 (59 to 65 kilodaltons). Of the three, the most important is the ZP-3, which functions as the spermatozoa-binding receptor and inducer of the acrosome reaction (see page 841); ZP-2 is believed to act as a secondary spermatozoa-binding protein, and ZP-1 has not yet been functionally characterized. In the light microscope, zona pellucida is clearly visible as a homogeneous and refractile layer that stains deeply with acidophilic stains and with the periodic acid–Schiff (PAS) reagents (Plate 92, page 872). It is first apparent when the oocyte, surrounded by a single layer of cuboidal or columnar follicle cells, has grown to a diameter of 50 m to 80 m.
Follicle cells undergo stratification to form the granulosa layer of the primary follicle.
Through rapid mitotic proliferation, the single layer of follicle cells gives rise to a stratified epithelium, the membrana granulosa (stratum granulosum), surrounding the oocyte. The follicle cells are now identified as granulosa cells. The basal lamina retains its position between the outermost layer of the follicle cells, which become columnar, and the connective tissue stroma.
During follicular growth, extensive gap junctions develop between granulosa cells. Unlike Sertoli cells in the testis, however, the basal layer of the granulosa cells does not possess elaborate tight junctions (zonulae occludentes), indicating the absence of a blood–follicle barrier. Movement of nutrients and small informational macromolecules from the blood into the follicular fluid is essential for normal development of the ovum and follicle.
Connective tissue cells form the theca layers of the primary follicle.
As the granulosa cells proliferate, stromal cells immediately surrounding the follicle form a sheath of connective tissue cells, known as the theca folliculi, just external to the basal
PRIMARY FOLLICLE stromal cells forming zona pellucida oocyte a follicle cells bbbbb FCFCFCFCFC FIGURE 23.4 • Early primary follicle. a. Schematic drawing of a primary follicle in an early stage of development. Note the formation of the zona pellucida between the oocyte and the adjacent follicle cells. A single layer of cuboidal follicle cells surrounds the growing oocyte. b. Photomicrograph of a primary follicle. Note the distinct layer of follicle cells (FC) surrounding the oocyte. 640.