Fig. 1. Ovarian follicles: the functional units of ovary for reproductive lifespan.

Along the hypothalamic-pituitary-ovarian axis, the hypothalamus secretes gonadotropin-releasing hormone (GnRH) which travels down to stimulate the pituitary gland which in turn secretes follicle stimulating hormone (FSH) and luteinizing hormone (LH). FSH and LH reach the ovaries in the bloodstream to signal the development of ovarian follicles to produce estrogen and progesterone during the follicular and luteal phase of the menstrual cycle. Estrogen rises steadily via a positive feedback loop to result in LH surge from the anterior pituitary gland, leading to ovulation. In a “young ovary”, in each cycle, several resting primordial follicles with immature ova are activated. They develop during folliculogenesis and normally only one ovarian follicle will be “selected” as the dominant follicle and eventually releases the mature ovum (ovulation). The ruptured follicle then transforms into the corpus luteum and degenerates to form the corpus albicans if no implantation occurred. Follicular supporting cells such as the granulosa and theca cells, and the corpus luteum provide endocrine support necessary for ovulation, preparation for implantation and pregnancy, with the release of estrogen and progesterone (symbolized as blue dots). As a woman ages, the finite pool of primordial follicles depletes during each ovulatory cycle and along with constant follicular atresia, results in the degeneration and loss of ovarian follicles and their oocytes, becoming the “aged ovary”. The “aged ovary” shrinks due to age-related fibrosis and releases little estrogen and progesterone due to the extremely low number of viable ovarian follicles.