The placenta may be dismissed as an afterthought in discussions about pregnancy. At long last it is beginning to get its due.
In the past three weeks, scientists have published three significant studies of this ephemeral organ. One gave a detailed analysis of the genes expressed, or converted into functioning proteins, in the placenta; another experimented with a way to silence that expression when it causes trouble. In the third, researchers created mini-placentas, three-dimensional clusters of cells, or organoids, that mimic the real thing in the lab, and can be used as models for studying.
At a recent meeting of the Human Placenta Project, teams of researchers showed off new techniques that enable the placenta to be studied in real time. That could help doctors diagnose dangerous complications in pregnancy — including pre-eclampsia, preterm birth and fetal growth restriction — early enough to intervene. It might help reveal why boys are much more vulnerable than girls to disorders of brain development.
“The missing link between complications during pregnancy and development of the fetal brain has been hiding in plain sight for a long time,” said Dr. Daniel Weinberger, director of the Lieber Institute for Brain Development in Baltimore. “It’s the placenta.”
An embryonic invasion
During the course of human pregnancy, the placenta grows from a few cells into an organ weighing more than 1 pound. It often is compared to an aggressive cancer. A more apt metaphor might be a military invasion, as 90 percent of the placenta is made up of cells from the fetus.
Early in gestation, the fertilized egg implants itself in the mother’s uterine lining and sends out a few cells to breach it. These foot soldiers produce proteins that disarm the mother’s defenses, destroy the smooth muscles that line her blood vessels and dilate and redirect the vessels to feed the embryo. As the placental beachhead grows, its cells specialize to do the work of heart, lungs, liver and kidneys until the fetus can fend for itself. Groups of cells exchange oxygen for carbon dioxide; provide nutrients and hormones; protect the fetus from harmful stress, germs and chemicals; and remove waste.
This incursion fails as often as 20 percent of the time, and when it does, it can cause severe complications. It may forecast trouble for the mother’s health later in life: pre-eclampsia can portend heart disease and stroke, and gestational diabetes can signal obesity and metabolic disease.
“There is nothing in medicine that can return so much on an investment as a healthy pregnancy and delivery, because that has years and years of impact later,” said Dr. George R. Saade, chief of obstetrics at the University of Texas Medical Branch. “And placental health is critical to the health of a pregnancy.”
The effects of stress
In the last few years Tracy Bale, director of the University of Maryland’s Center for Epigenetic Research in Child Health and Brain Development, has found the placenta of a male fetus is more vulnerable to external stress than the placenta of a female fetus. This vulnerability may transfer to the embryo, Bale said.
Male fetuses typically are larger than females throughout gestation, and have higher rates of spontaneous abortions, stillbirth, premature birth and neurodevelopmental conditions.
In May, Weinberger’s team at the Lieber Institute looked specifically at genes implicated in schizophrenia.
They found many of these genes are abundantly expressed in the fetal placenta, and are activated at even higher levels when the pregnancy is under stress; the effect is more dramatic in male fetuses than in females.
“We suggested that placentas of male fetuses seem to be more susceptible at a genetic level,” Weinberger said. “I’m very confident the same story is going to be there for autism, ADHD and other developmental behavioral problems.”
Womb with a view
Technological limitations obscured the central role the placenta plays in the health of baby and mother. The placenta is usually studied by dissecting it after delivery.
“That’s too late,” said Saade of the University of Texas. “It’s like studying cardiac disease or any other medical condition just by doing an autopsy.”
Problems with the placenta often begin in the spiral arteries of the mother — the arteries that the fetus commandeers to feed itself. If they are blocked or too narrow, the fetus may not get enough oxygen and nutrients, and the mother’s blood pressure may spike toward pre-eclampsia. This can begin as early as the first trimester. Few tools are available to diagnose it at that stage.
In 2014, the child-health division of the National Institutes of Health set out to find noninvasive methods to identify complications earlier.
An infusion of $80 million into placenta research prompted scientists to adapt technologies used in other fields, and has already provided insights into early pregnancy.
Some scientists are betting on magnetic resonance imaging scans, or MRIs, as the most sensitive detectors of placental problems. They are using a method that measures oxygen levels in the blood; it is quick and, so far, seems to catch problems as early as the second trimester.
MRI is not widely in use in obstetricians’ offices, in contrast with ultrasound machines, which would be a more practical option.
Traditional ultrasounds can show the structure and location of the placenta, not how well the organ is functioning. Advances over the past five years have sharpened the machine’s focus.
A team of scientists is using these advances in ultrasound to chart placental health in about 500 pregnant women, including 300 at high risk of complications.
They are collecting ultrasound data and blood samples from the women at eight time points during pregnancy to see which early features track with problems later on.