In a study using mice, researchers from the University of North Carolina School of Medicine found that a hormone, adrenomedullin, plays a crucial role in preventing the pregnancy complication preeclampsia. Surprisingly, this hormone protects women from preeclampsia when emitted by the fetus, not the mother, during the most critical times in pregnancy.
"We've identified the fact that the baby is important in protecting the mom from preeclampsia," said the study's senior author, Kathleen M. Caron, PhD, assistant dean for research at the UNC School of Medicine and an associate professor in the Department of Cell Biology and Physiology. "If the baby's cells are not secreting this hormone, the mother's blood vessels don't undergo the dilation that they should."
Preeclampsia affects roughly one in fifteen pregnancies. An important characteristic of the condition is that blood vessels in the placenta fail to enlarge, or dilate, to accommodate increased blood flow to the fetus. Untreated, it can threaten the life of both mother and baby.
"We really don't know that a pregnant woman is going to get preeclampsia until she has it," said Caron. Because the condition has numerous risk factors and causes, it's difficult for doctors to know which patients are at highest risk. "Identifying molecules that could predict preeclampsia would be really important."
The researchers studied mice that were genetically programmed to produce either reduced or increased levels of adrenomedullin. The study revealed that in a normal pregnancy, the fetus secretes adrenomedullin into the placenta during the second trimester, signaling special cells called "natural killer cells" to help dilate the mother's blood vessels and allow more blood to flow to the growing fetus.
The study is one of the first to identify an important chemical message sent from fetus to mother in the womb. Scientists understand more about the mom's side of the 'chemical conversation' that goes on between mother and baby, but much of the hormonal signaling in the placenta remains a mystery.
By identifying the key role of adrenomedullin, the research could pave the way to new methods for detecting and preventing preeclampsia. For example, adrenomedullin levels could potentially be used as a biomarker, or early indicator, to identify which patients might be predisposed to the condition. "Having a biomarker would be wonderful -- it could allow the physician to manage a woman differently in the early part of her pregnancy," said Caron.
As a next step, the researchers plan to build upon their mouse studies to examine patterns of adrenomedullin levels and preeclampsia in pregnant women.
This paper was published online ahead of print on May 1, 2013 in the Journal of Clinical Investigation (JCI). The paper will appear in the June 2013 print edition.
The study's co-authors include Manyu Li, Nicole M.J. Schwerbrock, Patricia M. Lenhart, Kimberly L. Fritz-Six, Mahita Kadmiel, Kathleen S. Christine, Scott T. Espenschied, Helen H. Willcockson and Christopher P. Mack of UNC and Daniel M. Kraus of Duke University Medical Center.
- Manyu Li, Nicole M.J. Schwerbrock, Patricia M. Lenhart, Kimberly L. Fritz-Six, Mahita Kadmiel, Kathleen S. Christine, Daniel M. Kraus, Scott T. Espenschied, Helen H. Willcockson, Christopher P. Mack, Kathleen M. Caron. Fetal-derived adrenomedullin mediates the innate immune milieu of the placenta. Journal of Clinical Investigation, 2013; DOI: 10.1172/JCI67039
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