The reserve of primordial follicles in the ovary starts at around 7 million and decreases to less than 300,000 at reproductive maturity. Between the first menstrual cycle (menarche) and the cessation of menstrual cycles (menopause), a woman typically ovulates about 450 follicles. By the time menopause occurs, there are less than 1000 primordial follicles remaining in the ovary. Most primordial follicles are lost due to follicular atresia, although a small number will begin to grow in waves. The rate at which primordial follicles die or develop determines a woman's reproductive lifespan. The onset of menopause is influenced by genetic factors and environmental factors, such as cigarette smoking. Premature ovarian insufficiency can occur if the reserve is depleted too rapidly.

Pituitary gonadotropins play a role in maintaining the overall health of the ovary and the ovarian reserve. However, the decision of a resting follicle to enter the growth phase is primarily influenced by intraovarian paracrine factors produced by the follicle cells and oocytes.

The gamete in primordial follicles is derived from oogonia that have undergone the first meiotic division, becoming primary oocytes. These primary oocytes go through most of prophase I over a period of 2 weeks before arresting in the diplotene stage. Meiotic arrest at this stage, which can last up to 50 years, is due to the lack of cell cycle proteins needed for meiosis completion. The nucleus of the oocyte, known as the germinal vesicle, remains intact during this stage.

The initial stage of follicular growth is preantral, which occurs before the formation of a fluid-filled antral cavity. One of the first visible signs of follicle growth is the presence of cuboidal granulosa cells. This marks the follicle as a primary follicle. As granulosa cells proliferate, they form a stratified epithelium around the oocyte, transforming the follicle into a secondary follicle. Once the secondary follicle acquires three to six layers of granulosa cells, it secretes paracrine factors that induce nearby stromal cells to differentiate into thecal cells. Thecal cells form a flattened layer around the follicle, and at this point, the follicle is considered a mature preantral follicle. It takes several months for a primary follicle to reach the mature preantral stage in humans.
Fig. 44.16). This reserve is reduced from a starting number of about 7 million to less than 300,000 follicles at reproductive maturity. Of these, a woman will ovulate about 450 between menarche (first menstrual cycle) and menopause (cessation of menstrual cycles). At menopause, less than 1000 primordial follicles are left in the ovary. Primordial follicles are lost primarily from death as a result of follicular atresia. However, a small subset of primordial follicles will enter follicular growth in waves. Because the ovarian follicular reserve represents a fixed finite number, the rate at which resting primordial follicles die or begin to develop (or both) will determine the reproductive life span of a woman. Age at the onset of menopause has a strong genetic component but is also influenced by environmental factors. For example, cigarette smoking significantly depletes the ovarian reserve. An overly rapid rate of atresia or development will deplete the reserve and give rise to premature ovarian insufficiency.
Pituitary gonadotropins maintain a normal ovarian reserve by promoting the general health of the ovary. However, the rate at which resting primordial follicles enter the growth process appears to be independent of pituitary gonadotropins. The decision of a resting follicle to enter the early growth phase is primarily dependent on intraovarian paracrine factors produced by both the follicle cells and oocytes.
The Gamete
In primordial follicles the gamete is derived from oogonia that have entered the first meiotic division; such oogonia are referred to as primary oocytes. Primary oocytes progress through most of prophase of the first meiotic division
Ovarian reserve ~300,000 primordial follicles at menarche Atresia ~270,000 primordial follicles Growth ~30,000 primordial follicles Atresia About 30,000 primary, secondary, or tertiary follicles Ovulation ~450 dominant follicles •Fig. 44.16 Fateofovarianfollicles.(ModifiedfromWhiteBA,PorterfieldSP.Endocrine Physiology. 4thed.Philadelphia:Mosby;2013.) (termed prophase I) over a 2-week period and then arrest in the diplotene stage. This stage is characterized by the decondensation of chromatin, which supports the transcription needed for oocyte maturation. Meiotic arrest at this stage, which may last for up to 50 years, appears to be due to “maturational incompetence,” or lack of the cell cycle proteins needed to support the completion of meiosis. The nucleus of the oocyte, called the germinal vesicle, remains intact at this stage.
The first stage of follicular growth is preantral, which refers to the development that occurs before the formation of a fluid-filled antral cavity. One of the first visible signs of follicle growth is the appearance of cuboidal granulosa cells. At this point the follicle is referred to as a primary follicle (see
Fig. 44.15 ). As granulosa cells proliferate, they form a multilayered (i.e., stratified) epithelium around the oocyte. At this stage the follicle is referred to as a secondary follicle (see
Fig. 44.15
Once a secondary follicle acquires three to six layers of granulosa cells, it secretes paracrine factors that induce nearby stromal cells to differentiate into epithelioid thecal cells. Thecal cells form a flattened layer of cells around the follicle. Once a thecal layer forms, the follicle is referred to as a mature preantral follicle (see
Fig. 44.15 ). In humans it takes several months for a primary follicle to reach the mature preantral stage.