Novel, Gene-Based Approaches Promise
Dramatic Change in Contraception
Supplement to Population Reports, New Contraceptive Choices, Series M, Number 19, April 2005

Scientific advances in gene research have brought about a better understanding of reproductive biology. Now they also offer new promise of safe and effective contraception. Recent findings could stimulate the development of contraceptives that target the genes controlling sperm and egg development or the proteins controlling fusion of sperm and egg.

Contraceptives based on these approaches are at least a decade away from reaching the market. They could, however, be dramatically different from current approaches to contraception. In particular, because many of the newly discovered genes and proteins function specifically in the reproductive tract, a contraceptive that alters or blocks these genes is unlikely to cause side effects by affecting other body systems (1, 2).

For women, several novel approaches appear possible. Of particular interest are contraceptive methods that target the molecules involved in the release of a mature egg during ovulation. Identifying specific enzymes responsible for the release of an egg would allow for the development of a contraceptive that would prevent ovulation but not disrupt endocrine function, thus avoiding hormonal side effects (1, 2).

Also promising are the female genes and proteins responsible for sperm-egg fusion. For example, researchers have discovered the zygote arrest 1 (ZAR1) gene, which plays a central role in the fusion of the sperm and egg pronuclei, the nucleuses containing genetic matter. In female mice lacking this gene, the pronuclei cannot fuse, resulting in infertility. Blocking ZAR1 would therefore be expected to have a contraceptive effect (3).

For men, too, the discovery of new genes and proteins appears to offer a promising approach. Scientists are studying the processes that enable sperm to penetrate an egg’s outer layer. If sperm can be prevented from whipping their tails or releasing the protein that enable them to enter the egg, they will be unable to fertilize the egg. For example, researchers have discovered a molecule in rats, Bin1b, existing only in the epididymis, where sperm normally mature and gain motility (the ability to move). Bin1b binds to the heads of sperm, inducing sperm motility. Blocking the action of this molecule could have a contraceptive effect because sperm would not be able to reach or penetrate the egg (4).

Genes that control the production and maturation of sperm also are possible new targets of contraception. If scientists can identify the genes responsible for sperm maturation, they could develop a drug to act on those genes and suppress sperm development.

Scientists are continually learning more about the genes and proteins that control fertility but have yet to understand fully how they can be manipulated to prevent pregnancy (1, 2). Still, given more resources, interest from more researchers, and more effective partnerships among academic research centers, nonprofit organizations, and pharmaceutical companies, an entirely new contraceptive method based on fundamental genetic processes could arrive within the next decade or two (1, 2).

Bibliography

1. INSTITUTE OF MEDICINE (IOM). New frontiers in contraceptive research: A blueprint for action. Nass, S.J. and Strauss, J.F., eds. Institute of Medicine (IOM), Jan. 21, 2004. 248 p.

2. STRAUSS, J.F. (University of Pennsylvania Medical Center) [New contraceptives] Personal communication, May 19, 2004.

3. WU, X., VIVEIROS, M.M., EPPIG, J.J., BAI, Y., FITZPATRICK, S.L., and MATZUK, M.M. Zygote arrest 1 (Zar1) is a novel maternal-effect gene critical for the oocyte-to-embryo transition. Nature Genetics 33(2): 187-191. Feb. 2003.

4. ZHOU, C.X., ZHANG, Y.L., XIAO, L., ZHENG, M., LEUNG, K.M., CHAN, M.Y., LO, P.S., TSANG, L.L., WONG, H.Y., HO, L.S., CHUNG, Y.W., and CHAN, H.C. An epididymis-specific beta-defensin is important for the initiation of sperm maturation. Nature Cell Biology 6(5): 458-464. May 2004.