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Zinc availability regulates exit from meiosis in maturing mammalian oocytes


Cellular metal ion fluxes are known in alkali and alkaline earth metals but are not well documented in transition metals. Here we describe major changes in the zinc physiology of the mammalian oocyte as it matures and initiates embryonic development. Single-cell elemental analysis of mouse oocytes by synchrotron-based X-ray fluorescence microscopy (XFM) revealed a 50% increase in total zinc content within the 12–14-h period of meiotic maturation. Perturbation of zinc homeostasis with a cell-permeable small-molecule chelator blocked meiotic progression past telophase I. Zinc supplementation rescued this phenotype when administered before this meiotic block. However, after telophase arrest, zinc triggered parthenogenesis, suggesting that exit from this meiotic step is tightly regulated by the availability of a zinc-dependent signal. These results implicate the zinc bolus acquired during meiotic maturation as an important part of the maternal legacy to the embryo.

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Figure 1: Synchrotron-based X-ray fluorescence microscopy reveals intracellular distribution of the transition elements in oocytes and early embryos.
Figure 2: The heavy-metal chelator TPEN disrupts asymmetric division of the oocyte, which can be rescued by exogenous zinc.
Figure 3: Zinc insufficient oocytes experience a meiotic block following telophase I.
Figure 4: Zinc supplementation following telophase-like arrest induces spontaneous activation of the zinc-insufficient oocyte.
Figure 5: Zinc-insufficient eggs can undergo a true fertilization event but show a delayed pronuclear stage and abnormal calcium oscillations upon activation.
Figure 6: Summary of results.


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The authors gratefully acknowledge J. Jozefik, S. Kiesewetter and D. Mackovic for animal care and concerns. We would also like to thank the P01 Histology Core (T. Wellington, director), the Analytical Services Laboratory and the Quantitative Bioelement Imaging Center in the Chemistry of Life Processes Institute at Northwestern University for reagents and discussions regarding sample processing. This work is supported by US National Institutes of Health grants P01 HD021921 and GM38784, the W.M. Keck Foundation Medical Research Award and the Chicago Biomedical Consortium Spark Award. A.M.K. was a fellow of the Reproductive Biology Training Grant HD007068. Use of the Advanced Photon Source at Argonne National Laboratory was supported by the Office of Basic Energy Sciences in the Office of Science of the US Department of Energy, under contract no. DE-AC02-06CH11357.

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A.M.K., T.V.O. and T.K.W. designed the research and wrote the manuscript. A.M.K. performed the research. S.V. provided XFM data analysis and technical support.

Corresponding authors

Correspondence to Thomas V O'Halloran or Teresa K Woodruff.

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The authors declare no competing financial interests.

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Supplementary Methods, Supplementary Scheme 1, Supplementary Figures 1–4 and Supplementary Tables 1–3 (PDF 9941 kb)

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Kim, A., Vogt, S., O'Halloran, T. et al. Zinc availability regulates exit from meiosis in maturing mammalian oocytes. Nat Chem Biol 6, 674–681 (2010).

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