Fluxes in cellular zinc concentration have recently been shown to control female gamete (egg) function, quality, and the meiotic cell cycle. For example, mammalian mouse oocytes acquire ca. 20 billion zinc atoms between prophase I and metaphase II (oocyte maturation), which controls cell cycle progression. At the time of fertilization, the egg undergoes zinc exocytosis events, resulting in the export of 15 billion zinc atoms. Similarly, during sperm maturation post-ejaculation, spermatozoa acquire 50 million zinc atoms during capacitation that are re-localized to the sperm head and midpiece. Labile zinc that is localized to the acrosome during uncapacitated and capacitated stages is exocytosed during the acrosome reaction as sperm prepare for fertilization. These parallel fluxes of zinc in the male and female gametes lead to our hypothesis: zinc signaling pathways regulated by zinc fluxes control oocyte and sperm maturation and zygote formation at the time of fertilization. A number of cell-permeable, small molecules have been deployed to manipulate and monitor zinc in the female and male gametes; however, they act both intracellularly and extracellularly and are not targetable. A newly developed chelator that has high affinity and selectivity will allow us to selectively chelate zinc outside the cell or in the cytosol following incubation or microinjection in order to study zinc’s role in oocyte maturation, sperm capacitation, and fertilization. This new membrane-impermeable zinc chelator has a broad application in the zinc bioinorganic community, e.g. beta-islet cells, neurons, mast cells. Here we will present information on the chelator and its chemistry and biological value in understanding the emerging roles for zinc fluxes in controlling the cell cycle in mammalian gametes and ultimately the processes of fertilization.

Zinc fluxes in control of gamete maturation, cell cycle, and fertilization

249th National Meeting (2015)

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