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.