Molecular Mechanisms of Cell Differentiation in Gonad Development

Rimon-Dahari, Nitzan, Yerushalmi-Heinemann, Lia, Alyagor, Liat, Dekel, Nava, Nitzan Rimon-Dahari, Lia Yerushalmi-Heinemann, Liat Alyagor, Nava Dekel

Rafal P. Piprek

The ovary, the female gonad, serves as the source for the germ cells as well as the major supplier of steroid sex hormones. During embryonic development, the primordial germ cells (PGCs) are specified, migrate to the site of the future gonad, and proliferate, forming structures of germ cells nests, which will eventually break down to generate the primordial follicles (PMFs). Each PMF contains an oocyte arrested at the first prophase of meiosis, surrounded by a flattened layer of somatic pre-granulosa cells. Most of the PMFs are kept dormant and only a selected population is activated to join the growing pool of follicles in a process regulated by both intra- and extra-oocyte factors. The PMFs will further develop into secondary pre-antral follicles, a stage which depends on bidirectional communication between the oocyte and the surrounding somatic cells. Many of the signaling molecules involved in this dialog belong to the transforming growth factor β (TGF-β) superfamily. As the follicle continues to develop, a cavity called antrum is formed. The resulting antral follicles relay on the pituitary gonadotropins, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) for their development. Most of the follicles undergo atretic degeneration and only a subset of the antral follicles, known as the dominant follicles, will reach the preovulatory stage at each reproductive cycle, respond to LH, and subsequently ovulate, releasing a fertilizable oocyte. The remaining somatic cells in the raptured follicle will undergo terminal differentiation and form the corpus luteum, which secretes progesterone necessary to maintain pregnancy.