Numerous irregular microvilli project from the oocyte into the perivitelline space between the oocyte and the surrounding granulosa cells as the zona pellucida is deposited (see Fig. 23.5). At the same time, slender processes from the granulosa cells develop and project toward the oocyte, intermingling with oocyte microvilli and, occasionally, invaginating into the oocyte plasma membrane. The processes may contact the plasma membrane but do not establish cytoplasmic continuity between the cells.
The secondary follicle is characterized by a fluid-containing antrum.
The primary follicle initially moves deeper into the cortical stroma as it increases in size, mostly through proliferation of the granulosa cells. Several factors are required for oocyte and follicular growth:  Follicle-stimulating hormone (FSH) Growth factors (e.g., epidermal growth factor [EGF],
When the stratum granulosum reaches a thickness of 6 to 12 cell layers, fuid-flled cavities appear among the granulosa cells (Fig. 23.6). As the hyaluronan-rich fluid called liquor folliculi continues to accumulate among the granulosa cells, the cavities begin to coalesce, eventually forming a single, crescent-shaped cavity called the antrum. The follicle is now identified as a secondary follicle or antral follicle (Plate 93, page 874). The eccentrically positioned oocyte, which has attained a diameter of about 125 m, undergoes no further growth. The inhibition of growth is achieved by the presence of a small, 1to 2-kilodalton peptide called oocyte maturation inhibitor (OMI), which is secreted by the granulosa cells into the antral fluid. A direct correlation is observed between the size of the secondary follicle and OMI concentration. The concentration is highest in small follicles and lowest in mature follicles. The follicle, which was 0.2 mm in diameter as an early secondary follicle when the fluid first appeared, continues to grow and reaches 10 mm or more in diameter.
Cells of the cumulus oophorus form a corona radiata around the secretory follicle oocyte.
As the secondary follicle increases in size, the antrum, lined by several layers of granulosa cells, also enlarges (Fig. 23.7). The stratum granulosum has a relatively uniform thickness except for the region associated with the oocyte. Here the granulosa cells form a thickened mound, the cumulus oophorus, which projects into the antrum. The cells of the cumulus oophorus that immediately surround the oocyte and remain with it at ovulation are referred to as the corona radiata. The corona radiata is composed of cumulus cells that send penetrating microvilli throughout the zona pellucida to communicate via gap junctions with microvilli of the oocyte. During follicular maturation, the number of surface microvilli of
FIGURE 23.6 • Secondary follicle. a. Schematic drawing of a secondary follicle showing the fluid-filled antrum, which arises by the coalescence of small fluid-filled cavities among the granulosa cells. Note that this actively growing follicle has many dividing granulosa cells. Call-Exner bodies appear at this stage. The wedge-shaped enlargement of the shadowed area depicts the relationship of the granulosa cells, basal lamina, and the theca interna and theca externa. The theca interna cells differentiate into highly vascularized, steroid-producing cells. The theca interna is surrounded by an outer layer of stromal cells called the theca externa. The basal lamina separates the granulosa cells from the theca interna. b. Photomicrograph of a secondary follicle. The antrum (A), filled with follicular fluid, is visible within the stratum granulosum (GC). Multiple layers of theca interna cells (TI) and theca externa cells (TE) can be seen outside the basal lamina of the secondary follicle. 85.