The oocyte zinc transporter Slc39a10/Zip10 is a regulator of zinc sparks during fertilization in mice

In all vertebrates studied to date, a rise(s) in intracellular calcium is indispensable for successful fertilization and further embryonic development. Recent studies demonstrated that zinc is ejected to the extracellular milieu, the ’zinc spark’, and follows the first few calcium rises of fertilization. However, the role of the zinc sparks in fertilization and development, and the supporting influx mechanism(s) are unknown. In this study, we focused on zinc transporters Zip10/Slc39a10 which was expressed in mouse oocytes through follicular development, and investigated the oocyte-specific deficient mice for Zip10 ( Zip10 ^d/d : Zip10 ^flox/flox Gdf9 ^Cre/+ ). Zip10 mRNA or ZIP10 protein was expressed throughout folliculogenesis in the oocyte or plasma membrane, respectively. The number of ovulated oocytes was examined in Zip10 ^d/d mice, and no change from the number of oocytes was observed. Zip10 ^d/d oocytes decreased zinc level in the oocytes, but did not affect maturation and metaphase II spindles formation. Fertilization-induced calcium oscillations were present in Zip10 ^d/d oocytes, but zinc sparks were not observed. Despite other events of egg activation proceeding normally in Zip10 ^d/d oocytes, embryo development into 4-cells and beyond was compromised. We show here for the first time that the zinc transporter ZIP10 contributes to zinc homeostasis in oocytes and embryos, highlighting the role of labile zinc ions in early development.