Physiologic Course of Female Reproductive Function: A Molecular Look into the Prologue of Life

Figure 2

Overview of gonadal differentiation and germ cell development. CYP26: retinoic acid hydroxylases; EM: extraembryonic mesoderm; FGF9: fibroblast growth factor-9; PGC: primordial germ cells. RA: retinoic acid. Syngamy yields a single totipotent cell, the zygote, which subsequently undergoes several proliferative and reorganizational processes. After gastrulation, arrangement into a three-layered embryonic structure, has occurred, nascent PGC undergo induction into pluripotent cells, specification, by EM. PGC also begin migration towards their final residence, the gonadal ridges, whilst simultaneously suffering epigenetic reprogramming essential for reactivation of totipotentiality. Afterwards, according to the sex chromosome load, both PGC and gonads undergo differentiation. In XY subjects, SRY induces differentiation of Sertoli cells, which thereafter drive testicular differentiation. Likewise, FGF9 and RA hydroxylases inhibit meiosis in these PGC, instead favoring mitosis and then cell cycle arrest until puberty. In contrast, in XX individuals it is FOXL2/RSPO1 signaling in ovarian primordia that drives development of female gonads and germ nest formation. RA then induces entry into meiosis and proliferation. These cells later suffer a wave of apoptosis which determines the final pool of primordial follicles, which remain arrested in meiosis I until puberty.