The placenta may be dismissed as “afterbirth,” deemed an afterthought in discussions about pregnancy and even relegated, literally, to the trash bin. But 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 all 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 laboratory and can be used as models for studying it.
In addition, at a recent meeting in Bethesda, Maryland, U.S., of the Human Placenta Project, several teams of researchers showed off sophisticated new techniques that enable the placenta to be studied in real time. That work could help doctors diagnose dangerous complications in pregnancy — including pre-eclampsia (a form of high blood pressure), preterm birth and foetal growth restriction — early enough to intervene. It might also help to reveal why boys are much more vulnerable than girls to disorders of brain development, including schizophrenia,
Attention-deficit/ hyperactivity disorder, or A.D.H.D., autism, dyslexia and Tourette syndrome.
“The missing link between complications during pregnancy and development of the foetal brain has been hiding in plain sight for a long time,” says Dr. Daniel R. Weinberger, director of the Lieber Institute for Brain Development in Baltimore, Maryland, U.S. “It’s the placenta.”
An embryonic invasion
Ninety per cent of the placenta is made up of cells not from the mother but from the foetus.
Early in gestation, the fertilised 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 defences, 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 specialise to do the work of the heart, lungs, liver and kidneys until the foetus can fend for itself. Groups of cells exchange oxygen for carbon dioxide; provide nutrients and hormones; protect the foetus from harmful stress, germs and chemicals; and remove waste.
This incursion fails as often as 20% of the time, and when it does, it can cause severe complications for the foetus, at birth and afterward. It may also forecast trouble for the mother’s health later in life: pre-eclampsia can portend heart disease and stroke, and gestational diabetes can signal later obesity and metabolic disease.
The effects of stress
Not all placentas develop equally. 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 that the placenta of a male foetus is more vulnerable to external stress than that of a female foetus. This vulnerability, in turn, may transfer to the embryo, Dr. Bale says. Male foetuses typically are larger than females throughout gestation, but they also have higher rates of spontaneous abortions, stillbirth, premature birth and neurodevelopmental conditions.
It’s not yet clear what makes female foetuses more resilient. But during the first trimester, 58 genes are expressed differently in male foetuses than in females, according to an analysis published in January, in the journal Biology of Sex Differences .
In May, Dr. Weinberger’s team at the Lieber Institute looked specifically at genes implicated in schizophrenia. They found that many of these genes are abundantly expressed in the foetal placenta, and are activated at even higher levels when the pregnancy is under stress; the effect is more dramatic in male foetuses than in females. “We suggested that placentas of male foetuses seem to be more susceptible at a genetic level,” Dr. Weinberger says. “I’m very confident the same story is going to be there for autism, A.D.H.D. and other developmental behavioural problems.”
Technological limitations have obscured the central role that the placenta plays in the health of both baby and mother. The placenta is a dynamic organ, but it usually has been studied by dissecting it after delivery.
Some scientists are betting on magnetic resonance imaging scans, or M.R.I.s, 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. Several teams worldwide are evaluating the technique, each in hundreds of women.
Other teams are trying to identify particles the placenta may release into the bloodstream because that could lead to a simple blood test for diagnosing problems. And one group of researchers is developing an oximeter, a device that quantifies the light reflected back through layers of fat as a measure of blood oxygen.
It will be at least five years before any of these tests makes their way to doctors’ offices. But when they are ready, they are likely to have a huge impact on obstetric practice, says Dr. Diana W. Bianchi, director of the National Institute of Child Health and Human Development. NY TIMES
