Born too soon  pg. 3

For Muglia, who came to Vanderbilt in 2009 from Washington University in St. Louis, the problems of prematurity resonated during the six months he spent as a pediatrics resident in the NICU at Children's Hospital Medical Center in Boston.

He was struck by the fact that the infant in the “enormous facility filled with isolettes and heating tables and sophisticated equipment of many kinds” were not sick because there was anything wrong with their developmental programs, but simply because they had been born too soon.

The biology fascinated him. “Who’s responsible for the timing of pregnancy – is it the mom, is it the baby, is it both? And how do we go about unraveling that biology?” he wondered.

To begin to get at these questions, Muglia and his Washington University colleagues turned to animal models – a common approach for exploring the physiology and genetics of biological processes. They studied various genetically altered mouse models, and they made good progress, Muglia says, in elucidating the pathway that is essential for birth timing in mice.

 
Louis J. Muglia, M.D., Ph.D.
Photo by Anne Rayner

The investigators know that mice (and other animals) experience a precipitous drop in the pregnancy-supporting hormone progesterone just before they deliver. And they know that an increase in inflammatory molecules causes the ovary to stop making progesterone. They were also able to pinpoint what makes the inflammatory molecules, and where they’re made.

The problem? In human pregnancy, the drop in progesterone that’s so essential to birth timing in the mouse doesn’t happen.

“So all those steps in mice that lead up to that fall in progesterone don’t predict what’s going to happen in humans,” Muglia says.

The studies did point to conserved pathways, Muglia points out. If progesterone falls during human pregnancy, the pregnancy will terminate; inflammatory molecules (prostaglandins) can be used to accelerate birth timing; and anti-inflammatory therapies can delay the progression of preterm labor (by blocking prostaglandin-mediated uterine contraction).

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