Like polystyrene packing around a glass vase, mammalian ova come individually wrapped in a protective cocoon, the zona pellucida (ZP). Besides shielding the unfertilized egg from damage, this translucent matrix of glycoproteins has several other vital functions.
For one thing, being species-specific, it prevents, say, a feline spermatozoon from penetrating a canine ovum. For another, it triggers the acrosome reaction, whereby the designated sperm cell's tip opens and elongates, like a hypodermic needle, to pierce and enter the ovum. Once this process takes place, the watchful ZP becomes a barrier that keeps out any and all other wannabe sperm from fertilizing that same egg.
Clearly, in view of all these functions favoring reproduction, the ZP has long attracted the attention of reproductive biologists as a potential site for contraceptive strategies. So far, its complexities have frustrated any such practical applications.
Among the still-unanswered questions: How far- reaching is the zona's species specificity? Are there enough homologies from one kind of mammal to another so that common antigens exist permitting immunocontraception? What genes actually encode the glycoproteins that anchor the 13-micron-thick ZP to the 100-micron ovum, and make up its intertwining, fibrous composition?
Now Zonagen Inc., a biotechnology company in The Woodlands, Texas, reports data with which, it states, "answering these questions should be possible."
The November issue of DNA Sequence--the Journal of Sequencing and Mapping carries an article by Zonagen's director of molecular biology, Jeffrey Harris, and Wayne State University co-authors, titled "Cloning and characterization of zona pellucida genes and cDNAs from a variety of mammalian species: The ZPA, ZPB and ZPC gene families."
All told, the authors analyzed and cloned full-length complementary zona DNA from eight species--rabbit, pig, cat, dog, cow, mouse, hamster and human.
"This report," says Joseph Podolski, Zonagen's president, "is the first to describe the presence of all three major zona pellucida genes within the ovaries of individual mammalian species." By labeling them A, B and C, the paper proposes that its nomenclature replace the current "very confusing" descriptions of ZP genes and proteins from the various mammalian species.
Cell biologist John Herr, director of the Center for Recombinant Gamete Vaccinology at the University of Virginia, in Charlottesville, observed, "Through a meticulous molecular biology sequencing effort, Zonagen has established a new method for organizing and characterizing the proteins enclosing the mammalian egg. Their work creates a simple, consistent nomenclature, which is already being adopted, and will likely become the standard used in the field."
Applying its own findings, Zonagen is developing technology for enlisting the immune system to generate an impenetrable layer of antibodies that bind to the egg, and prevent conception.
The company has applied for patents covering "all sequences of all ZP proteins reported in our journal publication," Podolski told BioWorld Today. "Active immunization with A-B-C determinants," he added, "will have a phsyical impact on the ovary, and has potential for an ideal contraceptive."
Zonagen has licensed this technology to Schering AG, of Berlin, Germany, for human applications worldwide, except India and China. Podolski said that his company exchanges data with India's premier researcher in population control, G. P. ("Pran") Talwar, and has found Chinese planners "extremely interested" in the ZP approach. "While it may take two or three years to reach the stage of clinical trials in U.S.," he said, "the opportunity could arise sooner than that in China."
Podolski sees human immunocontraception via the zona pellucida as "long-acting, minimally invasive and the potential choice of the next century." However, he observed, this represents only part of the opportunity. "Controlling the populations of broad mammalian species in general" is also in prospect. He cited by way of example, cutting down the proliferation of wild horses, deer and incipiently rabid raccoons, using bait containing an oral ZP immunogen- carrying vector. n
-- David N. Leff Science Editor
(c) 1997 American Health Consultants. All rights reserved.