Like polystyrene packing around a glass vase, mammalian ova comeindividually wrapped in a protective cocoon, the zona pellucida (ZP).Besides shielding the unfertilized egg from damage, this translucentmatrix of glycoproteins has several other vital functions.

For one thing, being species-specific, it prevents, say, a felinespermatozoon from penetrating a canine ovum. For another, ittriggers the acrosome reaction, whereby the designated sperm cell'stip opens and elongates, like a hypodermic needle, to pierce andenter the ovum. Once this process takes place, the watchful ZPbecomes a barrier that keeps out any and all other wannabe spermfrom fertilizing that same egg.

Clearly, in view of all these functions favoring reproduction, the ZPhas long attracted the attention of reproductive biologists as apotential site for contraceptive strategies. So far, its complexitieshave frustrated any such practical applications.

Among the still-unanswered questions: How far-reaching is the zona's species specificity? Are there enoughhomologies from one kind of mammal to another so that commonantigens exist permitting immunocontraception? What genes actuallyencode the glycoproteins that anchor the 13-micron-thick ZP to the100-micron ovum, and make up its intertwining, fibrouscomposition?

Now Zonagen Inc., a biotechnology company in The Woodlands,Texas, reports data with which, it states, "answering these questionsshould be possible."

The November issue of DNA Sequence--the Journal of Sequencingand Mapping carries an article by Zonagen's director of molecularbiology, Jeffrey Harris, and Wayne State University co-authors,titled "Cloning and characterization of zona pellucida genes andcDNAs from a variety of mammalian species: The ZPA, ZPB andZPC gene families."

All told, the authors analyzed and cloned full-length complementaryzona DNA from eight species--rabbit, pig, cat, dog, cow, mouse,hamster and human.

"This report," says Joseph Podolski, Zonagen's president, "is the firstto describe the presence of all three major zona pellucida geneswithin the ovaries of individual mammalian species." By labelingthem A, B and C, the paper proposes that its nomenclature replacethe current "very confusing" descriptions of ZP genes and proteinsfrom the various mammalian species.

Cell biologist John Herr, director of the Center for RecombinantGamete Vaccinology at the University of Virginia, in Charlottesville,observed, "Through a meticulous molecular biology sequencingeffort, Zonagen has established a new method for organizing andcharacterizing the proteins enclosing the mammalian egg. Theirwork creates a simple, consistent nomenclature, which is alreadybeing adopted, and will likely become the standard used in the field."

Applying its own findings, Zonagen is developing technology forenlisting the immune system to generate an impenetrable layer ofantibodies that bind to the egg, and prevent conception.

The company has applied for patents covering "all sequences of allZP proteins reported in our journal publication," Podolski toldBioWorld Today. "Active immunization with A-B-C determinants,"he added, "will have a phsyical impact on the ovary, and haspotential for an ideal contraceptive."

Zonagen has licensed this technology to Schering AG, of Berlin,Germany, for human applications worldwide, except India andChina. Podolski said that his company exchanges data with India'spremier researcher in population control, G. P. ("Pran") Talwar, andhas found Chinese planners "extremely interested" in the ZPapproach. "While it may take two or three years to reach the stage ofclinical trials in U.S.," he said, "the opportunity could arise soonerthan that in China."

Podolski sees human immunocontraception via the zona pellucida as"long-acting, minimally invasive and the potential choice of the nextcentury." However, he observed, this represents only part of theopportunity. "Controlling the populations of broad mammalianspecies in general" is also in prospect. He cited by way of example,cutting down the proliferation of wild horses, deer and incipientlyrabid raccoons, using bait containing an oral ZP immunogen-carrying vector. n

-- David N. Leff Science Editor

(c) 1997 American Health Consultants. All rights reserved.