Folliculogenesis is the development of ovarian follicles from primordial to tertiary under the stimulation of gonadotropins.

Ovarian follicles are oocytes and their supporting cells. They grow and develop in a process called folliculogenesis, which typically leads to ovulation of one follicle approximately every 28 days, along with death to multiple other follicles. The death of ovarian follicles is called atresia, and can occur at any point during follicular development. Recall that, a female infant at birth will have one to two million oocytes within her ovarian follicles, and that this number declines throughout life until menopause, when no follicles remain. As you'll see next, follicles progress from primordial, to primary, to secondary and tertiary stages prior to ovulation-with the oocyte inside the follicle remaining as a primary oocyte until right before ovulation.

Folliculogenesis begins with follicles in a resting state. These small primordial follicles are present in newborn females and are the prevailing follicle type in the adult ovary (Figure). Primordial follicles have only a single flat layer of support cells, called granulosa cells, that surround the oocyte, and they can stay in this resting state for years-some until right before menopause.After puberty, a few primordial follicles will respond to a recruitment signal each day, and will join a pool of immature growing follicles called primary follicles. Primary follicles start with a single layer of granulosa cells, but the granulosa cells then become active and transition from a flat or squamous shape to a rounded, cuboidal shape as they increase in size and proliferate. As the granulosa cells divide, the follicles-now called secondary follicles (see Figure)-increase in diameter, adding a new outer layer of connective tissue, blood vessels, and theca cells-cells that work with the granulosa cells to produce estrogens.

Within the growing secondary follicle, the primary oocyte now secretes a thin acellular membrane called the zona pellucida that will play a critical role in fertilization. A thick fluid, called follicular fluid, that has formed between the granulosa cells also begins to collect into one large pool, or antrum. Follicles in which the antrum has become large and fully formed are considered tertiary follicles (or antral follicles). Several follicles reach the tertiary stage at the same time, and most of these will undergo atresia. The one that does not die will continue to grow and develop until ovulation, when it will expel its secondary oocyte surrounded by several layers of granulosa cells from the ovary. Keep in mind that most follicles don't make it to this point. In fact, roughly 99 percent of the follicles in the ovary will undergo atresia, which can occur at any stage of folliculogenesis.

Folliculogenesis

(a) The maturation of a follicle is shown in a clockwise direction proceeding from the primordial follicles. FSH stimulates the growth of a tertiary follicle, and LH stimulates the production of estrogen by granulosa and theca cells. Once the follicle is mature, it ruptures and releases the oocyte. Cells remaining in the follicle then develop into the corpus luteum. (b) In this electron micrograph of a secondary follicle, the oocyte, theca cells (thecae folliculi), and developing antrum are clearly visible. EM × 1100. (Micrograph provided by the Regents of University of Michigan Medical School © 2012)

An ovarian follicle consists of a developing oocyte surrounded by one or more layers of cells called follicular cells. At the same time that the oocyte is progressing through meiosis, corresponding changes are taking place in the follicular cells. Primordial follicles, which consist of a primary oocyte surrounded by a single layer of flattened cells, develop in the fetus and are the stage that is present in the ovaries at birth and throughout childhood.

Beginning at puberty, follicle-stimulating hormone stimulates changes in the primordial follicles. The follicular cells become cuboidal, the primary oocyte enlarges, and it is now a primary follicle. The follicles continue to grow under the influence of follicle-stimulating hormone, and the follicular cells proliferate to form several layers of granulose cells around the primary oocyte. Most of these primary follicles degenerate along with the primary oocytes within them, but usually one continues to develop each month. The granulosa cells start secreting estrogen and a cavity, or antrum, forms within the follicle. When the antrum starts to develop, the follicle becomes a secondary follicle. The granulose cells also secrete a glycoprotein substance that forms a clear membrane, the zona pellucida, around the oocyte. After about 10 days of growth the follicle is a mature vesicular (graafian) follicle, which forms a "blister" on the surface of the ovary and contains a secondary oocyte ready for ovulation.