Veterinary Researchers Seek Secret to Reversing Birth Defects.(due to teratogen therapeutics)

2001 FEB 15 - (NewsRx.com) -- Fetal development is a highly choreographed process. But all too often it is disrupted when a mother is exposed to a teratogen - an agent known to cause a variety of birth defects.

In the United States alone, 150,000 babies are born with defects like these, making birth defects the leading cause of infant mortality. What if there was a way to reduce or even reverse these defects?

There is, says toxicologist Steven Holladay. He calls this area of study "immunoteratology." The name comes from the influence the mother's immune system can have in assuring fetal development remains on track.

Recognizing the tremendous impact this could have on the number of babies bom with birth defects every year, Holladay and his team of researchers at Virginia-Maryland Regional College of Veterinary Medicine set out to discover just how this magic really works. Scientists have reported that injecting pregnant mice with enough of an inert substance will alert and set into action one of the body's frontline immune cells called macrophages. Macrophages essentially engulf and break down what they see as foreign -- a process called phagocytosis.

In the past, other researchers had hypothesized that the macrophages were acting directly on the fetus. Under this scenario, the cells would cross the placenta from the mother, then find and eliminate abnormally developing cells in the fetus that were causing birth defects, such as cleft palates, digit anomalies, and neural tube defects affecting the brain and spinal cord. But that proved to be a dead end.

Holladay and colleague Lioudmila Sharova decided to turn down a different road. While their own tests clearly showed that immune stimulation did reduce birth defects in mice, they believed something other than maternal immune cells crossing the placenta was causing this phenomenon.

They knew that fundamental reproductive immunology suggests maternal immune cells don't routinely traffic across the placenta. This is in part because the fetus is genetically different from the mother and will be recognized by her immune cells as foreign, resulting in what is known as a negative graft-vs.-host rejection response in the fetus.