The follicle undergoes a movement towards the inner cortex during follicular development, getting closer to the vasculature of the ovarian medulla. Angiogenic factors released by the follicles induce the formation of one to two arterioles that create a vascular wreath around the follicle.
During the preantral stage, the oocyte begins to grow and produce cellular and secreted proteins. It secretes extracellular matrix glycoproteins known as ZP1, ZP2, and ZP3, which form the zona pellucida. The zona pellucida thickens and provides a binding site for sperm during fertilization. The granulosa cells and the oocyte maintain contact through the zona pellucida via cellular projections. The oocyte also secretes paracrine factors that regulate the growth and differentiation of follicle cells.
While granulosa cells express the FSH receptor during this stage, their growth primarily relies on factors from the oocyte. They do not produce ovarian hormones at this early stage. The thecal cells, similar to testicular Leydig cells, reside outside the nurse cells, express the LH receptor, and produce androgens. However, thecal cells do not express high levels of 17β-HSD. Thus, androstenedione is the main product of theca cells at this stage, rather than testosterone. Androstenedione production is minimal during this time.
Over a period of approximately 25 days, the small antral follicles grow from a diameter of 0.1 mm to 0.2 mm. As the granulosa epithelium increases to six to seven layers, fluid-filled spaces appear between cells and merge to form the antrum. These small antral follicles continue to grow for about 45 days, eventually becoming large recruitable antral follicles measuring 2 to 5 mm in diameter. This growth phase is characterized by a 100-fold increase in granulosa cells, swelling of the antral cavity, and the division of granulosa cells into two distinct populations: mural granulosa cells and cumulus cells.
Mural granulosa cells, also known as the stratum granulosum, form the outer wall of the follicle. The basal layer is attached to the basal lamina and in close proximity to the oocyte. The oocyte, initially arrested at prophase I, begins meiosis but lacks the required levels of proteins for its completion. As the oocyte grows, it synthesizes enough proteins to complete meiosis, but high levels of cAMP, generated by GPR3, maintain its arrest. A few hours before ovulation, the oocyte completes meiosis I and expels the first polar body. It has synthesized enough MAPK pathway proteins to arrest at metaphase II.
Follicular development is associated with an inward movement of the follicle from the outer cortex to the inner cortex, closer to the vasculature of the ovarian medulla. Follicles release angiogenic factors that induce development of one to two arterioles that form a vascular wreath around the follicle.
The Gamete
During the preantral stage, the oocyte begins to grow and produce cellular and secreted proteins. The oocyte initiates secretion of extracellular matrix glycoproteins called ZP1, ZP2, and ZP3 that form the zona pellucida (see
Fig. 44.15 ). The zona pellucida increases in thickness and provides a species-specific binding site for sperm during fertilization (see ). Importantly, granulosa cells and the oocyte maintain gap junctional contact via cellular projections through the zona pellucida. The oocyte also continues to secrete paracrine factors that regulate follicle cell growth and differentiation.
Granulosa cells express the FSH receptor during this period, but they are primarily dependent on factors from the oocyte to grow. They do not produce ovarian hormones at this early stage of follicular development. The newly acquired thecal cells are analogous to testicular Leydig cells in that they reside outside the epithelial “nurse” cells, express the LH receptor, and produce androgens. The main difference •Fig. 44.17 Developmentofanearlyantralfollicletoamaturepreovulatoryfollicle.(ModifiedfromWhiteBA,PorterfieldSP.Endocrine Physiology. 4thed.Philadelphia:Mosby;2013.) between Leydig cells and thecal cells is that thecal cells do not express high levels of 17β-HSD. Thus the major product of theca cells is androstenedione as opposed to testosterone. Androstenedione production at this stage is minimal.
Fig. 44.17 ) over a period of about 25 days, during which they grow from a diameter of about 0.1 mm to a diameter of 0.2 mm. Once the granulosa epithelium increases to six to seven layers, fluid-filled spaces appear between cells and coalesce into the antrum. Over a period of about 45 days, this wave of small antral follicles will continue to grow to large recruitable antral follicles that are 2 to 5mm in diameter. This period of growth is characterized by about a 100-fold increase in granulosa cells (from about 10,000 to 1,000,000 cells). It is also characterized by swelling of the antral cavity, which increasingly divides the granulosa cells into two discrete populations: mural granulosa cells and cumulus cells (see
Fig. 44.17
Mural granulosa cells (also called the stratum granulosum) form the outer wall of the follicle. The basal layer is adherent to the basal lamina and in close proximity to 802 SECTION8Berne & Levy Physiology Oogonium Primary oocyte arrested at prophase I Meiosis begins, but levels of proteins required for completion of meiosis are too low – oocyte arrests at prophase I.
As oocyte grows, it synthesizes enough proteins (e.g., CDK1, cyclin B) to complete meiosis (i.e., meiotic competence), but high cAMP levels generated by GPR3 actively maintain arrest.
A few hours before ovulation, the oocyte completes meiosis I and extrudes the first polar body. It has synthesized enough MAPK pathway proteins to arrest at metaphase II.