The Push to Understand the Placenta
By DENISE GRADY JULY 14, 2014
SAN FRANCISCO — Minutes after a baby girl was born on a recent morning at UCSF Medical Center here, her placenta — a pulpy blob of an organ that is usually thrown away — was packed up and carried off like treasure through a maze of corridors to the laboratory of Susan Fisher, a professor of obstetrics, gynecology and reproductive sciences.
There, scientists set upon the tissue with scalpels, forceps and an array of chemicals to extract its weirdly powerful cells, which storm the uterus like an invading army and commandeer a woman’s body for nine months to keep her fetus alive. The placenta is the life support system for the fetus. A disk of tissue attached to the uterine lining on one side and to the umbilical cord on the other, it grows from the embryo’s cells, not the mother’s. It is sometimes called the afterbirth: It comes out after the baby is born, usually weighing about a pound, or a sixth of the baby’s weight.
It provides oxygen, nourishment and waste disposal, doing the job of the lungs, liver, kidneys and other organs until the fetal ones kick in. If something goes wrong with the placenta, devastating problems can result, including miscarriage, stillbirth, prematurity, low birth weight and pre-eclampsia, a condition that drives up the mother’s blood pressure and can kill her and the fetus. A placenta much smaller or larger than average is often a sign of trouble. Increasingly, researchers think placental disorders can permanently alter the health of mother and child.
Given its vital role, shockingly little is known about the placenta. Only recently, for instance, did scientists start to suspect that the placenta may not be sterile, as once thought, but may have a microbiome of its own — a population of micro-organisms — that may help shape the immune system of the fetus and affect its health much later in life.
Dr. Fisher and other researchers have studied the placenta for decades, but she said: “Compared to what we should know, we know almost nothing. It’s a place where I think we could make real medical breakthroughs that I think would be of enormous importance to women and children and families.” The National Institute of Child Health and Human Development calls the placenta “the least understood human organ and arguably one of the more important, not only for the health of a woman and her fetus during pregnancy but also for the lifelong health of both.” In May, the institute gathered about 70 scientists at its first conference devoted to the placenta, in hopes of starting a Human Placenta Project, with the ultimate goal of finding ways to detect abnormalities in the organ earlier, and treat or prevent them.
Dr. Mirhan Kapidzic, with a placenta tissue sample, and Susan Fisher at a University of California, San Francisco, research center. Credit Jim Wilson/The New York Times
Seen shortly after a birth, the placenta is bloody and formidable looking. Fathers in the delivery room sometimes faint at the sight of it, doctors say. It is bluish or dark red, eight or nine inches across and about an inch thick in the middle. The side that faced the fetus is covered by a network of branching blood vessels, the umbilical cord emerging like a fat stalk. The side that faced the mother, glommed onto the uterine wall, looks raw and meaty. In some cultures, the organ has spiritual meaning and must be buried or dealt with according to rituals. In recent years in the United States, some women have become captivated by the idea of eating it — cooking it, blending it into smoothies, or having it dried and packed into capsules. Not much is known about whether this is a good idea.
When scientists describe the human placenta, one unsettling word comes up repeatedly: “invasive.” The organ begins forming in the lining of the uterus as soon as a fertilized egg lands there, embedding itself deeply in the mother’s tissue and tapping into her arteries so aggressively that researchers liken it to cancer. In most other mammals, the placental attachment is much more superficial. “A parasite upon the mother” is how the placenta is described in the book “Life’s Vital Link,” by Y. W. Loke, a reproductive immunologist. He goes on: “It has literally burrowed into the substance of her womb and is siphoning off nutrients from her blood to provide for the embryo.”
An Invader’s Intricacy
The placenta establishes a blood supply at 10 to 12 weeks of pregnancy. Ultimately, it invades 80 to 100 uterine vessels called spiral arteries and grows 32 miles of capillaries. The placental cells form minute fingerlike projections called villi, which contain fetal capillaries and come in contact with maternal blood, to pick up oxygen and nutrients and get rid of wastes. Spread out, the tissue formed to exchange oxygen and nutrients would cover 120 to 150 square feet. Every minute, about 20 percent of the mother’s blood supply flows through the placenta. The front line of the invasion is a cell called a trophoblast, from the outer layer of the embryo. Early in pregnancy, these cells multiply explosively and stream out like a column of soldiers.
“The trophoblast cells are so invasive from the get-go,” Dr. Fisher said. “They just blast through the uterine lining to get themselves buried in there.” They shove other cells out of the way and destroy them with digestive enzymes or secrete substances that induce the cells to kill themselves.Michael McMaster, a professor of cell and tissue biology at the University of California, San Francisco, said that failures of this early process probably happened fairly often. People often assume that miscarriages and other problems arise from the fetus itself, but he said, “it’s probably true that at this early stage, a lot of trophoblast malfunction can underlie pregnancy loss or future disease.”
Trophoblasts are so invasive that they will form a placenta almost anywhere, even if they land on tissue other than the uterus. Occasionally, pregnancies begin outside the uterus, in fallopian tubes or elsewhere in the abdomen, and the rapid, penetrating growth of the placenta can rupture organs. Placentas that form over a scar on the uterus, where the lining is thin or absent — say, from a previous cesarean section — can invade so deeply that they cannot be safely removed at birth, and the only way to prevent the mother from bleeding to death is to take out the uterus.
The Invasive Placenta
The placenta is an invasive organ that provides life support for a developing embryo.FERTILIZATION A fertilized human egg begins to divide. After about five days it forms a hollow ball of cells called a blastocyst: a sphere of specialized cells called trophoblasts, surrounding an inner cell mass that will eventually become the fetus.
IMPLANTATION Trophoblasts help embed the blastocyst in the mother’s uterine lining, then begin recruiting and remodeling her blood vessels to nourish the developing embryo. The invading cells will eventually form the placenta.
THE PLACENTA is the interface between mother and embryo. Fingerlike structures called villi provide a large surface area for the mother’s blood to surround but not mix with the embryo’s blood, providing oxygen and nutrients and removing waste.
Trophoblasts are a major focus of the research by Dr. Fisher’s team, and her laboratory also acts as a bank, providing cell and tissue samples to other researchers around the country. One staff member is a recruiter, charged with the delicate task of asking women in labor to donate their placentas for research.
Dr. Fisher’s lab discovered that as trophoblasts invade, they alter certain proteins on their surfaces, called adhesion molecules, to become more motile. Researchers later found that cancer cells do the same thing as they spread from a tumor to invade other parts of the body. Trophoblasts change in other ways, mimicking cells of the blood vessels they invade. The spiral arteries, which feed the lining of the uterus, become paved with trophoblasts instead of the woman’s own cells. This “remodeling” process dilates the arteries considerably to pour blood into the placenta and nourish the villi.
“When I first read this anatomy, I couldn’t believe the whole world wasn’t studying this,” Dr. Fisher said. Examining a micrograph of a remodeled artery, she said: “Look at the diameter of this vessel. It looks like some monster thing from the deep chasms of the sea.”
Stephanie Leong, part of Dr. Fisher’s team, asked a patient to donate her placenta. Credit Jim Wilson/The New York Times
What Can Go Wrong
Invasion and remodeling are essential: If they do not occur, the placenta cannot acquire enough of a blood supply to develop normally, and the results can be disastrous. One consequence can be pre-eclampsia, which affects 2 percent to 5 percent of pregnant women in the United States. Rates are higher in poor countries, particularly those in Africa. The condition brings high blood pressure and other abnormalities in the mother, and can be fatal. Pre-eclampsia is considered a placental disease: Most women with the illness have abnormally small placentas, and when pathologists examine them after the delivery, they often find blood clots, discolorations and a poorly developed blood supply. How and why the problem occurs is not entirely understood. For unknown reasons, the placenta does not form properly and cannot keep up with the demands of the growing fetus. The trophoblasts cannot fully change into artery cells and begin churning out an abnormal array of molecules that jack up the mother’s blood pressure and may damage her blood vessels.
The rising blood pressure may be an attempt to compensate by forcing more circulation to the placenta. But it backfires. The only treatment is to deliver the baby, which probably works because it also removes the placenta.
Placenta samples from a freezer at the University of California, San Francisco. “Compared to what we should know” about the placenta, Dr. Fisher said, “we know almost nothing.” Credit Jim Wilson/The New York TimesAt some hospitals, pathologists who specialize in the placenta examine the ones from troubled pregnancies or sickly newborns, looking for clues to what went wrong. Massachusetts General Hospital also keeps seemingly normal placentas in a refrigerator for about two weeks, until it is clear that the mother and the baby are healthy.
Dr. Drucilla J. Roberts, a placental pathologist there, said that relatively few hospitals had placental pathologists or the ability to train them. Nationwide, there are fewer than 100, she estimates. More are needed, she said. She and a colleague, Dr. Rosemary H. Tambouret, often examine specimens sent from other hospitals not equipped to do the work themselves.
“The placenta gives the answer in many term stillbirths,” Dr. Roberts said. Half of those deaths are never explained, but many of them involve abnormalities in the placenta, including infections or unusual conditions in which the mother’s immune system appears to have rejected the placenta. “I can’t tell you how important it is to the family just to have an answer,” she said. Knowing can help ease the guilt that many parents feel when a child is stillborn. The information can also tell doctors what to watch for in future pregnancies.
In one case, Dr. Roberts said, examining the placenta helped diagnose an immune incompatibility between the parents that had caused multiple stillbirths and miscarriages. The mother was treated and went on to have a healthy child.
Another placental pathologist, Dr. Rebecca Baergen, the chief of perinatal and obstetric pathology at NewYork-Presbyterian Hospital/Weill Cornell Medical Center, said that in some cases, particularly those involving fetal death or stillbirth, more could be learned from the placenta than from the fetus. She described a case in which a newborn was extremely small, had stunted limbs and did not survive. Doctors suspected a growth disorder, but bone samples revealed nothing.
The placenta was sent to Dr. Baergen. She found many problems with its blood supply and recommended a battery of tests for the mother. The tests found a hereditary blood disorder. The mother was treated and later gave birth to a healthy baby.
“The placenta has essentially been called the chronicle of intrauterine life,” she said. “It really tells the story of what’s been going on. It plays the role of many organs — liver, kidney, respiratory, endocrine. It can give you a lot of information about the baby’s and the mom’s health.”
A version of this article appears in print on July 15, 2014, on page D1 of the New York edition with the headline: The Mysterious Tree of a Newborn’s Life.