Uncovering the role of the placenta in pregnancy immune tolerance

Margaret Petroff believes that decoding additional secrets to immune tolerance could lead to treatment breakthroughs for a variety of conditions.

The placenta acts as the biological pathway between mother and fetus.

As millions of soldiers returned home after fighting in World War II, British biologist Peter Medawar was hard at work to help these veterans, many of whom had lost limbs in battle and were in need of intensive medical care.

Limb transplantation was dicey at best in the mid-20th century, with many procedures resulting in rejection. This influx of transplant patients highlighted an already serious issue that had baffled Medawar, who was determined to change the negative outcomes by focusing on the mechanism that caused rejection — the immune system.

His research eventually homed in on immune tolerance, the biological process that allows the host’s immune system to accept tissues from a genetically different individual. Medawar was awarded a Nobel Prize in 1960 for his work on this topic.

Today, there are still more questions than answers. Margaret Petroff, an associate professor in the Department of Pathobiology and Diagnostic Investigation at Michigan State University (MSU), believes that decoding additional secrets to immune tolerance could lead to treatment breakthroughs for a variety of conditions.

Petroff and her team are studying a form of immune tolerance familiar to many women — pregnancy.

“Pregnancy is something that, despite its prevalence, we still have a lot to learn about,” Petroff said. “We’re interested in understanding more about how the mother and the fetus live harmoniously. Half of the fetus’s genetic material is from the mother, and half is from the father. That half from the father is foreign to the mother, so we want to know how her immune system copes with it.”

Although blood between the mother and the fetus never mix, other genetic material does.

The placenta acts as the biological pathway between mother and fetus and is responsible for the transport of nutrients and oxygen. But the placenta also sheds genetic material that Petroff believes may be interacting with the mother’s immune system.

“We’ve historically believed that the physiological changes in the mother that occur during pregnancy have been mediated by hormones,” Petroff said. “But what we’re learning now is that there are a whole host of additional molecules from the placenta that are affecting the mother. We think that may be how the fetus communicates to the mother: ‘I’m not here to harm you in any way. I need you to continue my development.’”

In some cases, the mother’s immune system malfunctions during pregnancy. This can result in a number of complications, but one of the most common is preeclampsia. Petroff’s team has identified preeclampsia — with high blood pressure as the most common symptom — as a research priority because of its prevalence and that little is known about what causes it.

The disease is primarily apparent during a woman’s first pregnancy. Symptoms often do not appear until the third trimester, but they can also include swelling in the face and hands. A urine test to measure for elevated levels of protein is used to diagnose the condition.

Though the exact cause of the disease is unknown, Petroff said that the vesicles that carry genetic material to and from he placenta change with preeclampsia, and this may have a detrimental effect on both mother and fetus.

Preeclampsia occurs in roughly 5 to 10 percent of pregnancies in the United States, but the rate in the developing world is much higher because many women lack access to high-quality prenatal care.

The only cure for preeclampsia is delivery of the baby. If it is detected too early in the pregnancy for delivery, a series of precautionary actions may be taken. Left untreated, preeclampsia can result in death for both mother and fetus.

“Preeclampsia is a relatively common issue; it is a significant public health challenge,” Petroff said. “If we can better understand the function of the placenta during pregnancy and how that promotes immune tolerance, we can combat a number of pregnancy complications, including preeclampsia. This also has implications on many other areas of medicine such as transplantation.”

Petroff explained that animal agriculture could benefit from her group’s research as well.

“Whether we’re talking about humans or animals, in utero health is something that researchers in this field have learned much more about in recent years,” Petroff said. “We now know that if there is a complication during pregnancy, that person can deal with the consequences for the duration of his or her life. Learning more about how we can prevent these complications will be critical moving forward.”

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