be reviewed. hormone function as with most things related to the reproductive system, folliculogenesis is controlled by the endocrine system. five hormones participate in an intricate process of positive and negative feedback to regulate folliculogenesis. they are: gonadotropin-releasing hormone (gnrh) secreted by the hypothalamus two gonadotropins: follicle-stimulating hormone (fsh) luteinizing hormone (lh) estrogen progesterone gnrh stimulates the release of fsh and lh from the anterior pituitary gland that will later have a stimulatory effect on follicle growth (not immediately, however, because only antral follicles are dependent on fsh and lh). when theca cells form in the tertiary follicle the amount of estrogen increases sharply (theca-derived androgen is aromatized into estrogen by the granulosa cells). at low concentration, estrogen inhibits gonadotropins, but high concentration of estrogen stimulates them. in addition, as more estrogen is secreted, more lh receptors are made by the theca cells, inciting theca cells to create more androgen that will become estrogen downstream. this positive feedback loop causes lh to spike sharply, and it is this spike that causes ovulation. following ovulation, lh stimulates the formation of the corpus luteum. estrogen has since dropped to negative stimulatory levels after ovulation and therefore serves to maintain the concentration of fsh and lh. inhibin, which is also secreted by the corpus luteum, contributes to fsh inhibition. progesterone, secreted by the corpus luteum, inhibits the follicular growth and maintains the pregnancy. the endocrine system coincides with the menstrual cycle and goes through thirteen cycles (and thus thirteen lh spikes) during the course of normal folliculogenesis. however, coordinated enzyme signalling and the time-specific expression of hormonal receptors ensures that follicle growth does not become disregulated during these premature spikes. number of follicles "percentage of ovarian reserve related to increasing age. the curve describes the percentage of ovarian reserve remaining at ages from birth to 55 years, based on the adc model. 100% is taken to be the maximum ovarian reserve, occurring at 18–22 weeks post-conception. the percentages apply to all women whose ovarian reserve declines in line with our model (i.e. late and early menopause are associated with high and low peak ngf populations, respectively). we estimate that for 95% of women by the age of 30 years only 12% of their maximum pre-birth ngf population is present and by the age of 40 years only 3% remains. doi:10.1371/journal.pone.0008772.g005"recently, two publications have challenged the idea that a finite number of follicles are set around the time of birth. renewal of ovarian follicles from germline stem cells (originating from bone marrow and peripheral blood) was reported in the postnatal mouse ovary. studies attempting to replicate these results are underway, but a study of populations in 325 human ovaries found no supporting evidence for follicular replenishment. in 2010, researchers at the university of edinburgh determined that by the time women are 30 years old, only 10% of their non-growing follicles (ngfs) remain. at birth, women have all their follicles for folliculogenesis, and they steadily decline until menopause. depletion of the ovarian reserve as women (and mice) age, double-strand breaks accumulate in their primordial follicle reserve. these follicles contain primary oocytes that are arrested in prophase of the first cell division of meiosis. double-strand breaks are accurately repaired during meiosis by searching for, and building off of, the matching strand (termed “homologous recombinational repair”). titus et al. (2013) found that, as humans (and mice) age, expression of four key dna repair genes necessary for homologous recombinational repair declines in oocytes. they hypothesized that dna double-strand break repair is vital for the maintenance of oocyte reserve, and that a decline in efficiency of repair with age plays a key role in the depletion of the ovarian reserve (ovarian aging).