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, as well as the supporting influx mechanism(s), remains unknown. In this study, we focused on zinc transporters Slc39a10/Zip10 which were expressed in mouse oocytes through follicular development and investigated the oocyte-specific deficient mice for Slc39a10/Zip10 ( Slc39a10 cKO: Slc39a10 flox/flox Gdf9 Cre/+ ). Slc39a10 mRNA or SLC39A10/ZIP10 protein was expressed throughout folliculogenesis in the oocyte or plasma membrane, respectively. The number of ovulated oocytes was examined in Slc39a10 cKO mice, and no change from the number of oocytes was observed. Slc39a10 cKO oocytes decreased zinc level in the oocytes but did not affect maturation and metaphase II spindle formation. Fertilization-induced calcium oscillations were present in Slc39a10 cKO oocytes, but zinc sparks were not observed. Despite other events of egg activation proceeding normally in Slc39a10 cKO 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.