Typically viewed as healthy, antioxidants might have an unexpected side effect—they may cause fertility problems in women, suggests new research by Professor Nava Dekel and her team, of the Israel-based Weizmann Institute of Science's Department of Biological Regulation.

The research team recently published its findings in a journal called the Proceedings of the National Academy of Sciences.

Common antioxidants include vitamins C and E. These work by eliminating molecules called reactive oxygen species that are produced naturally in the body. Stress can cause these chemically active molecules to be overproduced; in large amounts, they damage cells indiscriminately. By neutralizing these potentially harmful substances, antioxidants may, theoretically, improve health and slow down the aging process.

But when Dekel and her research team applied antioxidants to the ovaries of female mice, the results were surprising: Ovulation levels dropped precipitously. That is, very few eggs were released from the ovarian follicles to reach the site of fertilization, compared with those in untreated ovaries.

To understand what lies behind these initial findings, the team asked whether it is possible that the process of ovulation might rely on the typically harmful substances, reactive oxygen species, destroyed by antioxidants.

Further testing in mice showed that this is, indeed, the case. In one experiment, for instance, Dekel and her team treated some ovarian follicles with luteinizing hormone, which is the physiological trigger for ovulation, and others with hydrogen peroxide, which is a reactive oxygen species.

The results showed hydrogen peroxide fully mimicked the effect of the ovulation-inducing hormone. This implies that reactive oxygen species that are produced in response to luteinizing hormone serve, in turn, as mediators for this physiological stimulus leading to ovulation.

Among other things, these results help fill in a picture that has begun to emerge in recent years of fertility and conception, in which it appears that these processes share a number of common mechanisms with inflammation. It makes sense, says Dekel, that substances which prevent inflammation in other parts of the body might also get in the way of normal ovulation, and so more caution should be taken when administering such substances.

Much of Dekel's research has focused on fertility. Her previous results are already helping some women become pregnant, but the new study has implications for those seeking the opposite effect. Dekel says, "On the one hand, these findings could prove useful to women who are having trouble getting pregnant. On the other, further studies might show that certain antioxidants might be effective means of birth control that could be safer than today's hormone-based prevention."

Dekel and her team now are planning further studies to investigate the exact mechanics of this step in the fertility process: to find out just how, when, and where antioxidants affect the ovaries, and to examine their effect on mice when administered in either food or drink.

In addition, they plan to collect data on the possible link between females taking antioxidant supplements and difficulty conceiving.

Dekel's research is supported by the M.D. Moross Institute for Cancer Research; the Jeanne and Joseph Nissim Foundation for Life Sciences Research; the Yeda-Sela Center for Basic Research; the Willner Family Center for Vascular Biology (Head); the Dwek Family Biomedical Research Fund; the Phyllis and Joseph Gurwin Fund for Scientific Advancement; and the J & R Foundation.

The Weizmann Institute of Science in Rehovot, Israel, is one of the world's top-ranking multidisciplinary research institutions. Noted for its wide-ranging exploration of the natural and exact sciences, the Institute is home to 2,700 scientists, students, technicians, and supporting staff.

Institute research efforts include the search for new ways of fighting disease and hunger, examining leading questions in mathematics and computer science, probing the physics of matter and the universe, creating novel materials, and developing new strategies for protecting the environment.