Journal
DEVELOPMENTAL CELL
Volume 25, Issue 1, Pages 106-112Publisher
CELL PRESS
DOI: 10.1016/j.devcel.2013.03.001
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Funding
- Merck-Serono Germany
- Natural Science and Medical Research Center (NMFZ) of the Johannes Gutenberg University Mainz
- Transgene Service, a core facility of the Interdisciplinary Center for Clinical Research (IZKF) Aachen within the Faculty of Medicine at RWTH Aachen University
- Deutsche Forschungsgemeinschaft Graduate Research School Biointerface [GK 1035]
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The zona pellucida (ZP) is a glycoprotein matrix surrounding mammalian oocytes. Upon fertilization, ZP hardening prevents sperm from binding to and penetrating the ZP. Here, we report that targeted gene deletion of the liver-derived plasma protein fetuin-B causes premature ZP hardening and, consequently, female infertility. Transplanting fetuin-B-deficient ovaries into wild-type recipients restores fertility, indicating that plasma fetuin-B is necessary and sufficient for fertilization. In vitro fertilization of oocytes from fetuin-B-deficient mice only worked after rendering the ZP penetrable by laser perforation. Mechanistically, fetuin-B sustains fertility by inhibiting ovastacin, a cortical granula protease known to trigger ZP hardening. Thus, plasma fetuin-B is necessary to restrain protease activity and thereby maintain ZP permeability until after gamete fusion. These results also show that premature ZP hardening can cause infertility in mice.
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