Mouse Morning-After Drug Might Fight Human Disease

Blocking the formation of new blood vessels in female mice can disrupt their reproductive cycles, including their ability to become pregnant. The finding, reported in the April issue of Nature Medicine, may lead to a new approach to treating endometriosis, uterine tumors, and other diseases in women.

Blood-vessel formation, or angiogenesis, already is a prime target for potential anticancer drugs now in clinical trials. But while these compounds are designed to block vessel growth in tumors, they may also impede the formation of new blood vessels in normal tissues during wound healing, menstruation, and pregnancy.

Robert D'Amato, a medical researcher at Children's Hospital in Boston, wondered if he could exploit this potential side effect to control fertility. He and his colleagues injected newly pregnant mice with AGM-1470, a compound now in anticancer trials. They found that the chemical disrupted the development of the placenta and the yolk sac, which provide blood and nutrients to the embryo. The embryos were unable to develop properly and were all reabsorbed by the mothers' bodies.

To see if AGM-1470 could prevent pregnancy, the researchers injected nonpregnant female mice with the compound every other day for 16 days. The treatment prevented the normal thickening and maturation of the endometrium--the lining of the uterus--and stunted the growth of the corpus luteum, a hormone-producing mass that forms in the ovaries during each estrus cycle.

Experts are excited about the study's implications for people. "It's so simple, but by using this one approach, you may be able to target a number of disease states," says Robert Barbieri, a gynecologist at Brigham and Women's Hospital in Boston. For instance, he says, an angiogenesis-blocker could stop the growth of uterine fibroids--benign tumors of the uterine lining--and the development of endometriosis, a painful and refractory condition in which endometrial cells grow outside the uterus. Further down the road, D'Amato says, drugs that block angiogenesis might even be candidates for a new female contraceptive.