Zinc as a Key Meiotic Cell-Cycle Regulator in the Mammalian Oocyte

Mammalian oogenesis is a discontinuous process that begins during fetal development, arrests at birth, and then resumes on a cyclical basis from puberty to menopause to produce fully mature oocytes that are competent for fertilization . Females are born with a fixed number of oocytes arrested at the prophase I stage of meiosis . This arrest is maintained until oocytes are selected to resume growth by gonadotropins, which are released from the pituitary upon entering puberty. At the time of ovulation, a fully grown oocyte completes maturation and arrests again at metaphase of meiosis II until fertilization occurs. Sperm binding triggers egg activation and release from metaphase II arrest. This entire process is tightly controlled, as it has a significant impact on egg quality and the developmental potential of the resulting embryo . The underlying mechanisms regulating oocyte meiotic entry, arrest, and exit—which can occur over a span of decades—have always been of great interest in the reproductive biology field, and many groundbreaking discoveries have revealed the existence of a dynamic network of hormones, receptors, kinases, and second messengers that control this process. Recent work has expanded this regulatory network to include the transition metal zinc , which adds a new level of complexity and fine-tuning to the regulation of the oocyte meiotic cell cycle . Dynamic accrual, sequestration, and exocytosis of zinc through controlled pathways are crucial for appropriate timing of the meiotic cell cycle as oocytes progress through maturation and activation. This work is important to our general understanding of oocytes and will have implications for reproductive interventions in the future.