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 in mouse oocytes, we investigated the role of zinc transporters Zip6/Slc39a6 and Zip10/Slc39a10. Zip10 mRNA or ZIP10 was expressed throughout folliculogenesis in oocyte or the plasma membrane, respectively. ZIP6 was also expressed in nuclear localization in oocytes and granulosa cells throughout folliculogenesis. The number of ovulated oocytes was examined in oocyte-specific Zip6 (Zip6^d/d: Zip6^flox/flox Gdf9^Cre/+) and Zip10 (Zip10^d/d: Zip10^flox/flox Gdf9^Cre/+) knockout mice, and no change was observed for either strain. Zip10^d/d oocytes matured and formed normal metaphase II spindles, but had lower labile zinc levels as suggested by the zinc indicator, Fluozin-3 intensity. The levels of zinc fluorescence intensity in the Zip6^d/d group were not different from the Zip6^f/f. Fertilization-induced calcium oscillations were present in both Zip6^d/d and Zip10^d/d oocytes, but zinc sparks were observed in Zip6^d/d but not in Zip10^d/d oocytes. Despite other events of egg activation proceeding normally in Zip10^d/d oocytes, embryo development into blastocysts was compromised. We show here for the first time that the zinc transporter ZIP10 contributes to zinc homeostasis in oocytes and embryos, highlighting the pivotal role of this divalent cation in early development.