title: Zinc sparks induce physiochemical changes in the egg zona pellucida that prevent polyspermy.
abstract: During fertilization or chemically-induced egg activation, the mouse egg releases billions of zinc atoms in brief bursts known as 'zinc sparks.' The zona pellucida (ZP), a glycoprotein matrix surrounding the egg, is the first structure zinc ions encounter as they diffuse away from the plasma membrane. Following fertilization, the ZP undergoes changes described as 'hardening', which prevent multiple sperm from fertilizing the egg and thereby establish a block to polyspermy. A major event in zona hardening is cleavage of ZP2 proteins by ovastacin; however, the overall physiochemical changes contributing to zona hardening are not well understood. Using X-ray fluorescence microscopy, transmission and scanning electron microscopy, and biological function assays, we tested the hypothesis that zinc release contributes to ZP hardening. We found that the zinc content in the ZP increases by 300% following activation and that zinc exposure modulates the architecture of the ZP matrix. Importantly, zinc-induced structural changes of the ZP have a direct biological consequence; namely, they reduce the ability of sperm to bind to the ZP. These results provide a paradigm-shifting model in which fertilization-induced zinc sparks contribute to the polyspermy block by altering conformations of the ZP matrix. This adds a previously unrecognized factor, namely zinc, to the process of ZP hardening.
authors.affiliation: The Chemistry of Life Processes Institute, Northwestern University, 2170 North Campus Drive, Silverman 4611, Evanston, IL 60208, USA. t-ohalloran@northwestern.edu.
authors.forename: Emily L
authors.identifier: 0000-0001-6604-3052
authors.initials: EL
authors.lastname: Que
authors.affiliation: Department of Obstetrics and Gynecology, Northwestern University, Feinberg School of Medicine, 303 East Superior Street, Lurie 10-121, Chicago, IL 60611, USA. tkw@northwestern.edu.
authors.forename: Francesca E
authors.initials: FE
authors.lastname: Duncan
authors.affiliation: The Chemistry of Life Processes Institute, Northwestern University, 2170 North Campus Drive, Silverman 4611, Evanston, IL 60208, USA. t-ohalloran@northwestern.edu and Department of Chemistry, Northwestern University, Evanston, IL 60208, USA.
authors.forename: Amanda R
authors.initials: AR
authors.lastname: Bayer
authors.affiliation: The Chemistry of Life Processes Institute, Northwestern University, 2170 North Campus Drive, Silverman 4611, Evanston, IL 60208, USA. t-ohalloran@northwestern.edu and Department of Molecular Biosciences, Northwestern University, Evanston, IL 60208, USA.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Philips
authors.affiliation: The Chemistry of Life Processes Institute, Northwestern University, 2170 North Campus Drive, Silverman 4611, Evanston, IL 60208, USA. t-ohalloran@northwestern.edu and Northwestern University Atomic and Nanoscale Characterization Experimental Center, Evanston, IL 60208, USA.
authors.forename: Eric W
authors.identifier: 0000-0002-8295-9834
authors.initials: EW
authors.lastname: Roth
authors.affiliation: The Chemistry of Life Processes Institute, Northwestern University, 2170 North Campus Drive, Silverman 4611, Evanston, IL 60208, USA. t-ohalloran@northwestern.edu and Northwestern University Atomic and Nanoscale Characterization Experimental Center, Evanston, IL 60208, USA.
authors.forename: Reiner
authors.initials: R
authors.lastname: Bleher
authors.affiliation: X-ray Science Division, Argonne National Laboratory, Argonne, IL 60439, USA.
authors.forename: Sophie C
authors.initials: SC
authors.lastname: Gleber
authors.affiliation: X-ray Science Division, Argonne National Laboratory, Argonne, IL 60439, USA.
authors.forename: Stefan
authors.initials: S
authors.lastname: Vogt
authors.affiliation: The Chemistry of Life Processes Institute, Northwestern University, 2170 North Campus Drive, Silverman 4611, Evanston, IL 60208, USA. t-ohalloran@northwestern.edu and Department of Obstetrics and Gynecology, Northwestern University, Feinberg School of Medicine, 303 East Superior Street, Lurie 10-121, Chicago, IL 60611, USA. tkw@northwestern.edu and Department of Molecular Biosciences, Northwestern University, Evanston, IL 60208, USA.
authors.forename: Teresa K
authors.initials: TK
authors.lastname: Woodruff
authors.affiliation: The Chemistry of Life Processes Institute, Northwestern University, 2170 North Campus Drive, Silverman 4611, Evanston, IL 60208, USA. t-ohalloran@northwestern.edu and Department of Chemistry, Northwestern University, Evanston, IL 60208, USA and Department of Molecular Biosciences, Northwestern University, Evanston, IL 60208, USA.
authors.forename: Thomas V
authors.initials: TV
authors.lastname: O'Halloran
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D005260:Female; D005306:Fertilization / Q000502:physiology*; D008297:Male; D051379:Mice; D010063:Ovum / Q000737:chemistry / Q000502:physiology*; D013094:Spermatozoa / Q000737:chemistry / Q000502:physiology*; D015032:Zinc / Q000737:chemistry / Q000378:metabolism*; D015044:Zona Pellucida / Q000737:chemistry / Q000502:physiology*
chemical_list: D015032:Zinc