Figure 1. Physical barriers to cell-to-cell communication in the ovarian follicle are established during folliculogenesis. During preantral growth, zona pellucida, the first significant barrier between the oocyte and follicular cells, is formed. This barrier between the germ and somatic cells results from the deposition of glycoproteins by the oocyte. For continuous maintenance of a cytoplasmic bridge between germ and somatic cells, the oocyte stimulates the granulosa cells to generate specialized cytoplasmic filaments connecting both cells – the transzonal projections (A). In antral growing follicles, a second significant barrier among follicular cells is formed – the antrum. Bilateral communication is maintained by paracrine signaling and extracellular vesicle traffic. Paracrine signaling of oocyte-secreted factors and transactivation of the EGF receptor by LH signaling drives follicle development and ovulation. Extracellular vesicles are secreted into the follicular fluid and are taken up by different cells types by a cargo delivery mechanism. The direct transfer of EVs-cargo from the follicular fluid to the oocyte remains elusive (B). CCs – cumulus cells; EVs – extracellular vesicles; GCs – granulosa cells; Theca – theca cells.