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The Feinstein Institute for Medical Research Discovers the Role ofProgesterone...

Each year, about 12 percent of pregnant women in the United States give birth before they complete their 37th week of gestation. Prematurity can result in health risks for both the newborn and the mother. Scientists have been trying to figure out what causes pre-term labor and identify ways to prevent it. Progesterone has been used successfully to push back labor and scientists at The Feinstein Institute for Medical Research (http://www.feinsteininstitute.org) have new evidence that the hormone may indeed modulate the fetal inflammatory response that is implicated in pre-term labor.

Working with Christine Metz, PhD, Head of the Laboratory of Medicinal Biochemistry, Nadav Schwartz, MD, decided to test whether progesterone (http://www.feinsteininstitute.org) directly suppressed pre-term labor and if so, how. It has long been known that infections can trigger pre-term labor, and it is the hypothesis that wayward inflammatory responses to bacterial infections provoke an early delivery. Maybe, they thought, progesterone suppresses the fetal inflammatory response.

While it is impossible to separate the fetal compartment from the maternal environment, the Feinstein researchers turned to fresh cord blood donated by mothers following the birth of their babies at North Shore Hospital. The hospital participates in the National Cord Blood Program but cord blood specimens that are too small are immediately slated for research. The Tissue Donation Program is part of the North Shore-LIJ Health System that collects cord blood samples following delivery.

In the latest study, they cull fetal cells (http://www.feinsteininstitute.org) from the cord blood and stimulate the cells with an infectious agent called LPS. This is a bacterial product used commonly in research to stimulate an inflammatory response. To test the power of progesterone in regulating this inflammatory response, they pre-treated the fetal cells with progesterone and measured whether there was a reduction in cytokine production. Cytokines are inflammatory factors released by the immune system. They measured two common cytokines, TNF (tumor necrosis factor) and IL-6 (Interleukin-6) implicated in pre-term labor. Progesterone reduced the inflammatory cytokines by 40 to 60 percent.

If this is taking place in the fetal environment, it could mean that progesterone treatment suppresses inflammation and prevents pre-term labor. The study was published recently in the American Journal of Obstetrics and Gynecology.

They also figured out how progesterone works to protect the fetal environment and stave off an early birth (http://www.feinsteininstitute.org). The process seems to be mediated by a reduction of cyclic AMP production, and progesterone actually increases cyclic AMP. These findings support the use of anti-inflammatory therapies that protect the breakdown of cyclic AMP to prevent pre-term labor induced by infections.

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