Zinc fluctuations regulate key steps in late oocyte and preimplantation embryo development; however, roles for zinc in preceding stages in early ovarian follicle development, when cooperative interactions exist between the oocyte and somatic cells, are unknown. To understand the roles of zinc during early follicle development, we applied single cell X-ray fluorescence microscopy, a radioactive zinc tracer, and a labile zinc probe to measure zinc in individual mouse oocytes and associated somatic cells within early follicles. Here, we report a significant stage-specific increase and compartmental redistribution in oocyte zinc content upon the initiation of early follicle growth. The increase in zinc correlates with the increased expression of specific zinc transporters, including two that are essential in oocyte maturation. While oocytes in follicles exhibit high tolerance to pronounced changes in zinc availability, somatic survival and proliferation are significantly more sensitive to zinc chelation or supplementation. Finally, transcriptomic, proteomic, and zinc loading analyses reveal enrichment of zinc targets in the ubiquitination pathway. Overall, these results demonstrate that distinct cell type–specific zinc regulations are required for follicle growth and indicate that physiological fluctuation in the localization and availability of this inorganic cofactor has fundamental functions in early gamete development.

锌的波动调节晚期卵母细胞和植入前胚胎发育的关键步骤；然而，当卵母细胞和体细胞之间存在协同相互作用时，锌在早期卵泡发育的前期阶段中的作用尚不清楚。为了了解锌在早期卵泡发育过程中的作用，我们应用单细胞 X 射线荧光显微镜、放射性锌示踪剂和不稳定的锌探针来测量早期卵泡内单个小鼠卵母细胞和相关体细胞中的锌。在这里，我们报告了早期卵泡生长开始时卵母细胞锌含量的显着阶段特异性增加和区室重新分布。锌的增加与特定锌转运蛋白表达的增加相关，其中包括卵母细胞成熟所必需的两种转运蛋白。虽然卵泡中的卵母细胞对锌可用性的显着变化表现出高度耐受性，但体细胞存活和增殖对锌螯合或补充明显更加敏感。最后，转录组、蛋白质组和锌负载分析揭示了泛素化途径中锌靶标的富集。总体而言，这些结果表明，卵泡生长需要不同的细胞类型特异性锌调节，并表明这种无机辅助因子的定位和可用性的生理波动在早期配子发育中具有基本功能。