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A push for new knowledge about labor

By Laura Stephenson Carter

No one fully understands the intricate dance of the hormones that trigger labor. Two DMS researchers thought they'd come close recently and submitted a paper detailing their findings to the Journal of Clinical Investigation. But the discovery-that a muscle relaxant triggers labor's forceful uterine contractions-was so surprising that the journal's reviewers asked the investigators to perform additional experiments to confirm the finding. They did so, and the paper was published a few months ago.

Trigger: The researchers-graduate student Kristina Fetalvero and vascular surgery researcher Kathleen Martin, Ph.D.-weren't surprised their discovery was controversial. It's long been known that prostacyclin, a fatty acid, is present in low levels in the uterus during pregnancy and spikes before labor starts. But until now no one suspected it might actually trigger labor.

Dartmouth ob-gyn Roger Young, M.D., Ph.D., recalls attending a meeting where Fetalvero and Martin presented their data -showing that prostacyclin both relaxes and enhances the contraction of smooth muscle cells in blood vessels and in the uterus. "I simply thought they were wrong," laughs Young. "I thought they were right in vascular, but that it would be a different result in uterine cells."

Soon the researchers made a believer out of him. Young, who is now at the University of Vermont, became a partner in the study. He provided tiny strips of uterine tissue, which he obtained from 21 volunteers about to undergo elective c-sections. The slices-two per patient-were attached to 400-milligram weights and suspended in test tubes.

The weights helped the tissue maintain the ability to contract, which it would rapidly lose in a normal culture dish. One strip of each pair was treated with prostacyclin for 48 hours; the other was untreated. Then all the strips were stimulated with oxytocin, a muscle contractant present in labor. The treated samples underwent much stronger contractions than the untreated ones. The researchers determined that the prostacyclin had upregulated proteins that stimulate the contraction of smooth muscle cells.

Signals: The study has limitations, however, says Fetalvero, who's now a postdoctoral fellow at Novartis in Cambridge, Mass. Uterine tissue outside the body can't be stimulated by the signals that normally come from the fetus and hormones in the body. "All of these work together to trigger the labor phase," she says. But studying uterine tissue in the lab "is the next best thing to understanding human labor right now."

The study, which was funded by the National Institutes of Health, has implications for preventing preterm delivery, which has been increasing and now occurs in about 12% of pregnancies, says Young. "It makes it more incumbent on us to find at least one therapy that seems to work," he points out. "Right now we have none."

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