The follicle is the functional unit of the mammalian ovary and serves as a tightly controlled microenvironment where granulosa cells nurture the growth and maturation of the oocyte. Early events in follicular development are autonomous of the hypothalamic-pituitary-gonadal axis and are instead controlled by local factors that are used in bidirectional communication between oocytes and somatic cells. While gonadotropins will eventually become the principle regulators of follicular growth, maturation, and ovulation, it is becoming appreciated that their actions are achieved through interactions with local intraovarian signals. The use of genetic tools developed in murine models has led to the discovery of vast networks of oocyte-, granulosa cell-, thecal cell-, and stromal cell-derived factors that govern gonadotropin-independent follicular development. Many of these discoveries from rodent models have proved broadly applicable to other mammalian systems. We summarize current knowledge of how local juxtacrine and paracrine signaling pathways control follicular development and interact with gonadotropin signaling to ensure female fertility and reproductive health.
