Study shows battle between mother and fetus

A team of Yale researchers has discovered the mechanisms behind a potentially fatal conflict between mother and fetus during pregnancy.

As a fetus attempts to acquire more of its mother’s resources during pregnancy, it must attack arteries in its mother’s uterus while diverting the mother’s immune surveillance system. Harvey Kliman, a researcher of obstetrics and gynecology at the Yale School of Medicine, discovered the mechanism that allows the fetus to distract the mother’s immune system by causing limited cell death and inflammation. The failure to do so results in a condition called preeclampsia, in which the mother’s blood pressure can increase to fatal levels.

Published in the Oct. 11 issue of the journal Reproductive Sciences, the study may help improve clinical tests for early detection of preeclampsia, Kliman said.

“Symptoms [of preeclampsia] are usually only recognized late in pregnancy, but we believe the pathology starts much earlier,” said Frederick Schatz, another reproductive sciences researcher at Yale who was not involved in the study. “There’s good evidence for several markers that might allow obstetricians to find and monitor preeclamptic women early on.”

Preeclampsia results when a fetus’s placenta, which is derived from the father’s genes, makes cells that attack the mother’s arteries in the uterus on behalf of the fetus, Kliman said. This attack increases blood flow into the baby’s placenta, bringing it more nutrients. These details have been known, but Yale researchers have now shed light on the details of the battle.

In order for the invasive cells to circumvent the mother’s white blood cells, the placenta secretes the protein PP13 into the mother’s blood as a diversion, Kliman said. White blood cells are the foot soldiers of the human immune system and although they would normally defend the arteries in the uterus, the white blood cells instead attack the decoy PP13, leaving the arteries unprotected. The entire area around the PP13 secretion becomes inflamed and filled with the mother’s dead white blood cells, while the placental cells destroy the arteries, increasing blood flow and nutrient supply to the baby, Kliman said.

“The finding was completely unexpected,” Kliman said. “For such death and destruction to be a normal part of pregnancy is shocking.”

In the absence of PP13, the attacking cells are destroyed and the intact arteries prevent enough blood from reaching the baby. In response, the placenta releases signals that increase the mother’s blood pressure in an attempt to increase blood flow, causing the mother to develop preeclampsia.

Kliman said uncovering this mechanism may lay the basis for providing diagnosis and treatment options to pregnant women who develop preeclampsia. Doctors may now be able to detect women who are at risk for preeclampsia long before symptoms emerge, he said.

Schatz said early detection will help obstetricians monitor preeclamptic women and minimize symptoms, but added that effective cures have yet to be found.

“In developed countries, the women can receive treatment, but it seems they’re more susceptible to cardiovascular problems later in life.” Schatz said. “In underdeveloped countries, the high blood pressure gets much worse and the women die.”

Schatz said that until a treatment becomes available, obstetricians will have to find a balance between taking care of the mother and ensuring that the baby is not born too prematurely.

Preeclampsia affects 5 percent of all pregnancies, according to the Preeclampsia Foundation. The only known treatments for preeclampsia are abortion or premature delivery of the baby.

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