Regulation of Sperm Development by Zinc: Insights from Quantitative Subcellular X-Ray Fluorescence Imaging

This talk will focus on the zinc fluxes that regulate sperm activation.Quantitative single cell X-ray fluorescence microscopyat APS beam lines and the Bionanoprobe at Argonne NationalLaboratory reveals a critical regulatory role changes in zinccontent and subcellular localization. Recent applications ofsynchrotron based X-ray fluorescence microscopy (XFM) areat the heart of a number of breakthroughs in our understandingof the most fundamental aspects of biology. In conjunctionwith label-free, high-resolution ptychographic imaging, XFMis greatly enhancing the ability of chemists and biologists tointerrogate chemical changes in subcellular compartmentsduring developmental processes. Our studies of zinc fluxes insperm include live cell studies in confocal fluorescence experiments,ICP-MS and radiotracer analysis. We find that fullsperm function in fertilization requires the movement of zincions between subcellular compartments: millions of zinc ionmust be taken up by sperm and accumulate in the nucleus.These movements of zinc must occur in a tightly regulatedtime over minutes to hours and sperm cells that do not undergothese fluxes are much less successful in fertilization ofmouse eggs in vitro. This work reveals that fluctuations in theconcentration and binding sites of zinc, like calcium and phosphorous,act as conductors of information in biological signalingnetworks. As sensitivity and resolution of XFM methodsincrease, we anticipate that quantitative imaging of the fluxesof other abundant inorganic cofactors, such as copper, potassium,sodium, iron and manganese will likewise reveal newmechanisms in biology.