Zinc dynamics regulate early ovarian follicle development

Zinc fluctuations regulate key steps in late oocyte and pre-implantation 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 fluo-rescence microscopy, a radioactive zinc tracer, and a labile zinc probe to measure zinc in individual mouse oocytes and asso-ciated somatic cells within early follicles. Here, we report a significant stage-specific increase and compartmental redistri-bution in oocyte zinc content upon the initiation of early fol-licle 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 avail-ability, somatic survival and proliferation are significantly more sensitive to zinc chelation or supplementation. Finally, tran-scriptomic, 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 func-tions in early gamete development.

Automated summary

By using various techniques, such as single cell X-ray fluorescence microscopy and radioactive zinc tracer, this study reveals an increase in zinc content in oocytes during early follicle growth which is correlated with the expression of specific zinc transporters. Moreover, it is found that somatic survival and proliferation are more sensitive to changes in zinc availability compared to oocytes. Overall, these findings indicate the importance of cell type-specific zinc regulations in early follicle development and suggest that zinc plays fundamental roles in early gamete development.