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February 2001
Vol. 4, No. 2, p. 12.
news in brief
On egg shells
Zona destruction.
Zona destruction. As it nears the egg, chemicals in the female reproductive tract capacitate the sperm, making it capable of fertilization. Breaking through the outer layer of follicle cells , the sperm’s acrosome lyses, releasing enzymes that break down the glycoproteins forming the zona pellucida. The sperm’s membrane then fuses with that of the ovum, and the sperm head is drawn inside.
The zona pellucida (ZP) is the thick outer surface of a developed mammalian ovum and forms the last layer of defense between an ovum and incoming sperm. It is composed of a variety of glycoproteins that are being studied for use as contraceptive vaccines. Experiments carried out on mammals using different ZP proteins as immunocontraceptive antigens have generated some concern. Permanent disruption of the normal menstrual cycle, an effect that can be correlated to ovarian pathology, has been observed. Serious side effects aside, it has also been unclear which class of ZP proteins, if any, would be suitable candidates for further vaccine studies.

Recently, researchers at Zonagen, a Texas pharmaceutical company that develops reproductive medicine products, performed experiments on cynomolgus monkeys and baboons to determine the efficacy of one of the three classes of recombinant human ZP proteins, ZPB, as an immunocontraceptive antigen (J. Reprod. Fertil. 2000, 120, 19–32). The scientists, M. L. Martinez and J. D. Harris, performed a breeding study on cynomolgus monkeys vaccinated with the three ZP proteins, ZPA, ZPB, and ZPC, alone and in various combinations. To test the experiment’s repeatability in another primate species, they performed a similar study on baboons, in this case using the ZP proteins individually rather than in combination.

The researchers reported that primates vaccinated with recombinant human ZPB protein became infertile for 9 to >20 months. The primates immunized with other ZP proteins and the control animals all became pregnant before any of the ZPB-immunized primates did. Furthermore, the most commonly observed side effect was temporary disruption of the menstrual cycle when the antibody titer was highest. “This is the first study in which a recombinant ZP protein has consistently induced infertility in a primate without permanent disruption of the normal menstrual cycle,” the researchers note.

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