Abstract
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.
| Original language | English (US) |
|---|---|
| Article number | 102731 |
| Journal | Journal of Biological Chemistry |
| Volume | 299 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 2023 |
Funding
This research applied resources of the Advanced Photon Source, a U.S. Department of Energy (DOE) Office of Science User Facility, operated for the DOE Office of Science by Argonne National Laboratory under Contract No. DE-AC02-06CH11357. Extraordinary facility operations were supported in part by the DOE Office of Science through the National Virtual Biotechnology Laboratory, a consortium of DOE national laboratories focused on the response to COVID-19, with funding provided by the Coronavirus CARES Act. Proteomic analysis was performed at the Northwestern Proteomics Core Facility, supported by NCI CCSG P30CA060553 awarded to the Robert H Lurie Comprehensive Cancer Center , instrumentation award ( S10OD025194 ) from NIH Office of Director , and the National Resource for Translational and Developmental Proteomics supported by P41GM108569 . We thank Northwestern University Quantitative Bio-element Imaging Center for elemental analysis assistance. We further thank A. Crawford, A. Nowakowski for advice and experimental assistance, and E. Maxey for XFM beamline support. This research was supported by NIH grants R01GM115848 (T. V. O. and T. K. W.), R01GM038784 (T. V. O.), P41GM135018 (T. V. O.), and the Thomas J. Watkins Endowment (T. K. W.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Keywords
- follicle
- folliculogenesis
- germ cell
- granulosa cell
- oocyte
- zinc
ASJC Scopus subject areas
- Molecular Biology
- Biochemistry
- Cell Biology