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J. Biol. Chem., Vol. 280, Issue 13, 12721-12731, April 1, 2005

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Human Sperm Do Not Bind to Rat Zonae Pellucidae Despite the Presence of Four Homologous Glycoproteins^*

Tanya Hoodbhoy, Saurabh Joshi, Emily S. Boja¶, Suzannah A. Williams||, Pamela Stanley||, and Jurrien Dean

From the Laboratory of Cellular and Developmental Biology, NIDDK and the ^¶Laboratory of Biophysical Chemistry, NHLBI, National Institutes of Health, Bethesda, Maryland 20892 and the ^||Department of Cell Biology, Albert Einstein College of Medicine, New York, New York 10461

The specificity of sperm-egg recognition in mammals is mediated primarily by the zona pellucida surrounding ovulated eggs. Mouse sperm are quite promiscuous and bind to human eggs, but human spermatozoa will not bind to mouse eggs. The mouse zona pellucida contains three glycoproteins, ZP1, ZP2, and ZP3, which are conserved in rat and human. The recent observation that human zonae pellucidae contain a fourth protein raises the possibility that the presence of four zona proteins will support human sperm binding. Using mass spectrometry, four proteins that are similar in size and share 62–70% amino acid identity with human ZP1, ZP2, ZP3, and ZP4/ZPB were detected in rat zonae pellucidae. However, although mouse and rat spermatozoa bind to eggs from each rodent, human sperm bind to neither, and the presence of human follicular fluid did not alter the specificity of sperm binding. In addition, mutant mouse eggs lacking hybrid/complex N-glycans or deficient in Core 2 O-glycans were no more able to support human sperm binding than normal mouse eggs. These data suggest that the presence of four zona proteins are not sufficient to support human sperm binding to rodent eggs and that additional determinants must be responsible for taxon-specific fertilization among mammals.

Received for publication, December 2, 2004 , and in revised form, January 27, 2005.

^* The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

To whom correspondence should be addressed: Laboratory of Cellular and Developmental Biology, NIDDK, Bldg. 50, Rm. 3128, National Institutes of Health, Bethesda, MD 20892-8028. Tel.: 301-594-1405; Fax: 301-496-5239; E-mail: tanyah{at}intra.niddk.nih.gov.

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