The ovarian follicle development is a complex process involving the coordination of many factors that regulate the growth and differentiation of the female gamete and the surrounding somatic components.

Follicular development starts from a pool of inactive primordial follicles. Primordial follicles are generated from primordial germ cells (PGs) and surrounding undifferentiated somatic cells that migrate to the genital ridge where they undergo mitosis cycles creating the germ cell cyst. This process is under the control of many factors such as BMPs, NANOG, OCT4, and FIGα.

Following the germ cell cyst, mitosis is arrested and germ cells start meiosis giving rise to the primary oocytes. Primary oocyte and somatic cells form the primordial follicle in which oocytes arrest in the diktyate stage of meiosis I and are surrounded by primordial GCs. This process is regulated by estrogens and a number of growth factors (Ttf and GEFF) and protein (FOXL2 and NOBOX). The activation of primordial follicles to develop in primary follicles is a dynamic process strictly controlled by PI3K/AKT pathway. Primordial follicles are the total germ cells reservoir of a woman and are continuously activated during the entire life to initiate the folliculogenesis. The expression of two oocyte factors (SOHLH1 and NOBOX) is crucial for primordial follicles activation and progression to the primary follicle. During this stage, the oocytes grow and the surrounding GCs begin mitotic divisions. The number of GCs increases as well as the number of cuboidal GCs layers around the oocyte, and the basal lamina expands. GCs express anti-Mullerian hormone (AMH) to control the number of primordial follicles being active. Primary follicles turn into secondary follicles under the control of local intra-ovarian factors produced by oocyte and GCs, such as GDF9 and BMP15. The early stages of follicular development are hormones-independent even if GCs express the stimulating hormone receptors (FSHR). Intra-ovarian paracrine factors play their role also during the formation of pre-antral follicle, but the expression of receptors for FSH and LH demonstrates that the follicles become sensitive to gonadotropins at this stage. During the formation of antral follicles, GCs show high proliferative capacity, giving rise to the particular antral multi-layer structure, forming the antral cavity. Many factors are involved in these phases of follicular development including Activin-A and Inhibinα. During the antral stage, GCs create the complex network of interaction with oocyte and the other GCs by GAP junctions that are essential for cellular communications during all phases of follicular development. Finally, the antral follicle reaches its late stage with the formation of antrum, and GCs differentiate into mural cells (MCs) and cumulus cells (CCs). MCs surround the wall of the follicles and are mainly involved in steroidogenic function, while CCs remain strictly associated to oocyte creating particular gap junctions in a specialized structure, namely, the cumulus-oocyte complex (COC). This particular structure allows the oocyte to acquire the competence to continue meiotic division and the capability to be fertilized. MCs and CCs are differentially regulated by oocyte factors and LH activity, and in particular, oocytes regulate the CCs metabolic activity. Gap junctions are extremely important for the bidirectional communications between oocyte and CCs, which are physically separated by the zona pellucida. These highly specialized junctions allow the passage of many molecules from CCs to oocyte, such as amino acids and metabolites, and their activity is essential to oocyte development and competence. During the ovulation process, CCs expansion is regulated both by oocyte and LH activity [5].

Many pathways have been reported to be activated in the inter-communications between GCs and oocyte, and it is known that alterations in GCs are responsible for oocyte maturation arrest or low quality. The deregulation of GCs translates into follicle microenvironment disruption with oocyte competence and maturation alterations. Furthermore, GCs alterations have been linked to women infertility phenotypes. Transcriptomic analysis of GCs could thus be useful to uncover new biomarkers of oocyte quality and competence [6].