The oocyte zinc transporterSlc39a10/Zip10is 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 Zip6/Slc39a6 and Zip10/Slc39a10 both of which are expressed in mouse oocytes through follicular development, and investigated the oocyte-specific deficient mice for Zip6 ( Zip6 d/d : Zip6 flox/flox Gdf9 Cre/+ ) and 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. ZIP6 protein was also expressed in the nuclear localization in the oocytes and granulosa cells throughout folliculogenesis. The number of ovulated oocytes was examined in Zip6 d/d and Zip10 d/d mice, and no change from the number of oocytes was observed for either strain. Zip10 d/d oocytes decreased zinc level in the oocytes, but did not affect maturation and metaphase II spindles formation. The levels of zinc fluorescence intensity in the Zip6 d/d oocytes were not different from the Zip6 f/f oocytes. Fertilization-induced calcium oscillations were present in both Zip6 d/d and Zip10 d/d oocytes, but zinc sparks were not observed in Zip10 d/d oocytes. 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. Submission information The zinc transporter, Slc39a10/Zip10 , is required for the zinc sparks of fertilization in mice.