Battle between the placenta and uterus could help explain preeclampsia
A battle that brews in the mother’s womb between the father’s biological goal to produce the biggest, healthiest baby possible vs. the mother’s need to live through delivery might help explain preeclampsia, an often deadly disease of pregnancy. The fetus must be big enough to thrive, yet small enough to pass through the birth canal. In a new study, Yale researchers describe the mechanism that keeps these conflicting goals in balance.
The findings are published in the October 11, 2011 online issue of Reproductive Sciences.
The battle is waged between the mother’s uterus and the baby’s placenta, which is made up of cells called trophoblasts that are controlled by the father. In the study, led by Harvey J. Kliman, M.D., research scientist in the Department of Obstetrics, Gynecology & Reproductive Sciences at Yale School of Medicine, researchers observed how the placenta tricks the mother so she doesn’t attack the trophoblasts that are trying to increase the flow of her blood into the placenta. If this placental deception doesn’t work the mother may develop preeclampsia, a condition that results in high blood pressure and protein in the mother’s urine. The only known cure for preeclampsia is delivery of the baby.
The placenta’s job is to get nutrients from the mother during pregnancy. Kliman explained that in a normal pregnancy, specialized invasive trophoblasts leave the placenta and invade the mother’s tissues to attack and destroy the walls of her blood vessels. This allows the most blood possible to enter the placenta, resulting in a big baby.
But the mother’s own “soldiers,” called lymphocytes, are constantly looking to destroy the invasive trophoblast cells. The placenta in turn appears to trick the mother by creating a diversion to occupy her lymphocytes.
Preeclampsia is a disorder that occurs only during pregnancy and the postpartum period and affects both the mother and the unborn baby. Affecting at least 5-8% of all pregnancies, it is a rapidly progressive condition characterized by high blood pressure and the presence of protein in the urine. Swelling, sudden weight gain, headaches and changes in vision are important symptoms; however, some women with rapidly advancing disease report few symptoms.
Typically, preeclampsia occurs after 20 weeks gestation (in the late 2nd or 3rd trimesters or middle to late pregnancy), though it can occur earlier. Proper prenatal care is essential to diagnose and manage preeclampsia. Pregnancy Induced Hypertension (PIH) and toxemia are outdated terms for preeclampsia. HELLP syndrome and eclampsia (seizures) are other variants of preeclampsia.
Globally, preeclampsia and other hypertensive disorders of pregnancy are a leading cause of maternal and infant illness and death. By conservative estimates, these disorders are responsible for 76,000 maternal and 500,000 infant deaths each year.
The placenta creates this diversion by secreting a protein called placental protein 13 (PP13), also known as galectin 13, into the mother’s blood where it travels through her veins into the uterus below the placenta. There the PP13 leaves the veins where it triggers the mother’s immune system to react and attack. The entire area around these veins becomes a mass of inflammation and dead cells, called necrosis.
Is pre-eclampsia the same as gestational high blood pressure?
No. Many pregnant women develop mild high blood pressure that is not pre-eclampsia. This is known as gestational high blood pressure or pregnancy-induced high blood pressure.
Gestational high blood pressure is new high blood pressure that comes on for the first time after the 20th week of pregnancy. Doctors can confirm this type of high blood pressure if you do not go on to develop pre-eclampsia during your pregnancy and if your blood pressure has returned to normal within six weeks of you giving birth. If you have gestational high blood pressure, you do not have protein in your urine when it is tested by your midwife or doctor during your pregnancy. With pre-eclampsia, you have high blood pressure plus protein in your urine, and sometimes other symptoms and complications listed below.
Note: some women may be found to have new high blood pressure after 20 weeks of pregnancy. At first, they may not have any protein in their urine on testing. However, they may later develop protein in their urine and so be diagnosed with pre-eclampsia. You are only said to have pregnancy-induced hypertension if you do not go on to develop pre-eclampsia during your pregnancy.
“We realized that these zones of necrosis are likely occupying the mother’s soldiers while the invasive trophoblasts sneak into her arteries, leading to more blood flow to the placenta and a bigger baby,” said Kliman. “We believe that maintaining this balance could be the key to a healthy pregnancy free from preeclampsia.”
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Other authors on the study include Marei Sammar, Yael Grimpel, Stephanie Lynch, Kristin Milano, Elah Pick, Jacob Bejar, Ayala Arad, James Lee, Hamutal Meiri and Ron Gonen.
The study was funded by a research grant from the European Union (FP6-grant # 037244, project title Pregenesys), the Finland Israel R&D Fund grant #41256 (Eureka – 3808 RPT), and the Yale University Reproductive and Placental Research Unit.
Citation: Reproductive Sciences doi: 10.1177/1933719111424445 (October 2011)
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