Scientists at Cincinnati Children’s hospital and the University of Cincinnati have discovered a remarkable association between risk for placenta accreta in pregnant women with a gene mutation that prevents healthy formation of “natural killer” cells (NK).
NK cells are a type of white blood cell that helps the body fight off cancer tumours and viral infections.
Placenta accreta is one of the most dangerous risks faced by expectant mothers. It occurs when the placenta grows too deeply into the uterine wall.
In normal childbirth, the placenta detaches from the uterine wall shortly after childbirth. With placenta accreta, part or all of the placenta remains attached that it cannot be removed without causing massive, sometimes fatal bleeding. This can cause severe blood loss after delivery. In many cases, the emergency surgery is needed to save the mother’s life that could leave her unable to have any more children.
During an experiment the researchers observed a lower yield in mice due to unsuccessful pregnancies.The researchers found that the mice had retained placentas, reflective of human accreta—a condition rarely seen in mice.
On further investigation the researchers found that the mice carried a mutation in a protein called Gab3 which prevented normal NK cell expansion in the uterus.
The disrupted NK cells then failed to turn off the process that allows the growing embryo to attach to tissues inside the uterus. This process, called trophoblast invasion, normally continues until about 20 weeks of pregnancy. But for women with accreta, the invasion continues much longer.
“For normal placental development to occur, the growth of foetal cells must be held in check by NK cells,”says Kasper Hoebe, PhD, Scientist at Cincinnati Children’s Division of Immunobiology .
“Our studies showed that in the absence of Gab3, NK cell function in the placenta is impaired, leading to an over-invasion of foetal cells into the uterus.”
Many people do not know about placental accreta, even though the number of women diagnosed with it has quadrupled since the 1980s to 1 in every 272 births. This increase is reportedly associated with a rise in C-section rate.
“This is a huge issue for maternal health,” says study co-author Helen Jones, PhD, an expert in placenta research at Cincinnati Children’s. “Currently, the only way to diagnose accreta is to spot it mid-pregnancy on ultrasound, usually after 18 to 20 weeks. Many women never know they have it until they arrive at the hospital for labor and delivery.”
The discovery could lead to a reliable biomarker to detect the condition that may help to proactively treat accreta.
Much more research must be done before women can be tested to determine if they have malfunctioning NK cells, and if an NK cell transplant would be safe and effective. NK cells have been transplanted to treat people with certain forms of cancer, but the potential impacts on a pregnancy are not yet known.
If future studies confirm that women facing accreta also have malfunctioning NK cells, it may become possible to prevent over-attachment and reduce the need for fertility-ending hysterectomies, says Jones.
The study was published in Science Immunology.