Proteasomal Interference Prevents Zona Pellucida Penetration and Fertilization in Mammals

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Proteasomal Interference Prevents Zona Pellucida Penetration and Fertilization in Mammals

Please use this identifier to cite or link to this item: http://hdl.handle.net/10355/8599

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Title: Proteasomal Interference Prevents Zona Pellucida Penetration and Fertilization in Mammals
Author: Sutovsky, Peter; Manandhar, Gaurishankar; McCauley, Tod C.; Caamaño, Jose Nestor; Sutovsky, Miriam; Thompson, Winston E.; Day, B.N.
Date: 7/14/2004
Publisher: Society for the Study of Reproduction, Inc.
Citation: Biology of Reproduction. 71(5):1625-1637. 2004.
Abstract: The ubiquitin-proteasome pathway has been implicated in the penetration of ascidian vitelline envelope by the fertilizing spermatozoon (Sawada et al., Proc Natl Acad Sci U S A 2002; 99:1223-1228). The present study provides experimental evidence demonstrating proteasome involvement in the penetration of mammalian zona pellucida (ZP). Using porcine in vitro fertilization as a model, penetration of ZP was completely inhibited by specific proteasomal inhibitors MG-132 and lactacystin. Three commercial rabbit sera recognizing 20S proteasomal core subunits b-1i, b-2i, a-6, and b-5 completely blocked fertilization at a very low concentration (i.e., diluted 1/2000 to 1/8000 in fertilization medium). Neither proteasome inhibitors nor antibodies had any effects on sperm-ZP binding and acrosome exocytosis in zona-enclosed oocytes or on fertilization rates in zona-free oocytes, which were highly polyspermic. Consistent with a possible role of ubiquitin-proteasome pathway in ZP penetration, ubiquitin and various a and b type proteasomal subunits were detected in boar sperm acrosome by specific antibodies, immunoprecipitated and microsequenced by MALDITOF from boar sperm extracts. Antiubiquitin-immunoreactive substrates were detected on the outer face of ZP by epifluorescence microscopy. This study therefore provides strong evidence implicating the ubiquitin-proteasome pathway in mammalian fertilization and zona penetration. This finding opens a new line of acrosome/ZP research because further studies of the sperm acrosomal proteasome can provide new tools for the management of polyspermia during in vitro fertilization and identify new targets for contraceptive development.
URI: http://hdl.handle.net/10355/8599
ISSN: 0006-3363

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