Marine Science Institute, The University of Texas at Austin, 750 Channelview Dr., Port Aransas, TX, 78373, USA.
Sci Rep. 2020 Sep 24;10(1):15673. doi: 10.1038/s41598-020-72515-4.
The zinc transporter ZIP9 (SLC39A9) was recently characterized as a membrane androgen receptor in various teleost and mammalian cell models. ZIP9 shows the highest expression in ovaries of teleosts, a tissue in which both androgen signaling and zinc dynamics have significant roles. To examine the role of ZIP9 in ovarian physiology, we generated a ZIP9-mutant zebrafish strain using a CRISPR/Cas9 system. zip9 females showed significant reductions in fecundity, embryo viability, and growth of their offspring compared to wildtype (WT) fish. Furthermore, a high proportion of zip9 eggs failed to undergo normal chorion elevation during activation. In WT eggs, zinc was detected in cortically-localized vesicles which underwent exocytosis upon activation. zip9 eggs showed abnormal cortical vesicle development and had a significantly depressed activation-induced zinc release compared to WT eggs. Moreover, pharmacologically sustained elevation of zinc in WT eggs prior to activation resulted in abnormal chorion elevation similar to that observed in zip9 eggs. These results indicate that ZIP9 is essential for proper zinc modulation during zebrafish egg activation and presents the first evidence of zinc modulation during egg activation in a non-mammalian species.
锌转运蛋白 ZIP9（SLC39A9）最近被鉴定为各种硬骨鱼和哺乳动物细胞模型中的膜雄激素受体。ZIP9 在硬骨鱼的卵巢中表达最高，卵巢是雄激素信号和锌动态都具有重要作用的组织。为了研究 ZIP9 在卵巢生理学中的作用，我们使用 CRISPR/Cas9 系统生成了 ZIP9 突变的斑马鱼品系。与野生型（WT）鱼相比，zip9 雌性的繁殖力、胚胎存活率和后代生长显著降低。此外，大量的 zip9 卵在激活过程中未能正常进行卵壳隆起。在 WT 卵中，锌被检测到在皮质定位的小泡中，这些小泡在激活时发生胞吐作用。与 WT 卵相比，zip9 卵显示出异常的皮质小泡发育，并且激活诱导的锌释放显著降低。此外，在激活前用药物持续升高 WT 卵中的锌水平会导致类似于在 zip9 卵中观察到的异常卵壳隆起。这些结果表明，ZIP9 对于斑马鱼卵激活过程中适当的锌调节是必不可少的，并首次证明了非哺乳动物物种中卵激活过程中的锌调节。
