REPRODUCTIVE BIOLOGY

Gearing up for a closer look at the human placenta Workshop participants build an agenda for research on this oft-ignored bridge between mother and fetus By Jocelyn Kaiser, Potomac, Maryland

PHOTO: CNRI/SCIENCE PHOTO LIBRARY

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placenta sustained you and every person ever born for 9 months, serving as your lungs and kidneys and pumping out hormones while you developed in the womb. Problems with this diskshaped mass of tissue can contribute to everything from preterm births to diseases of middle age. Yet when a baby is born, hospitals usually throw the placenta away. “It’s the least understood human organ,” says Alan Guttmacher, director of the National Institute of Child Health and Human Development (NICHD) in Bethesda, Maryland. “A large part of the scientific community never thinks about the placenta at all.” He and others hope to change that, however, by rallying researchers and funders around a project to better understand the underappreciated organ. At an NICHD-sponsored workshop here last week, some 70 researchers laid out their ideas for a Human Placenta Project, including ways to better monitor the placenta during a pregnancy, and drugs to bolster it when it falters. The human placenta forms primarily from tissue that originates in the outer layer of fetal cells that surround an early embryo. Early in pregnancy, these trophoblasts invade the uterine wall and later develop a

complex network of tiny projections called villi, which contain fetal blood vessels. This treelike structure of villi absorbs oxygen and nutrients from maternal blood; fetal waste and carbon dioxide meanwhile diffuse into the maternal bloodstream. Other specialized cells link the developing placenta to the umbilical cord. To avoid rejection by the mother’s immune system, the placenta employs various tricks, such as not expressing certain proteins. The placenta’s role during pregnancy is “an incredibly interesting biological time” that offers lessons for everything from cancer to organ transplantation, says physician-scientist Kimberly Leslie of the University of Iowa in Iowa City. A malfunctioning, too small, or weakly attached placenta can starve the fetus, stunting its growth. Such problems can also contribute to preeclampsia, or pregnancyrelated high blood pressure, a condition that occurs in up to 6% of pregnancies and can require premature delivery of a baby. Adult diseases, too, ranging from heart disease to insulin resistance, seem to be linked to abnormal placenta morphology for poorly understood reasons (Science, 7 June 2013, p. 1160). During recent strategic planning at NICHD, researchers concluded that the placenta deserved closer study. “It came up repeatedly,” Guttmacher says. He expects

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that the Human Placenta Project will focus on understanding both the normal and abnormal placenta in real time during the course of pregnancy. It will also look for possible interventions—for example, a drug that would spur the growth of a too-small placenta. Some at the workshop hope to adapt ultrasound and magnetic resonance imaging techniques now used to study the heart and brain to measure blood flow and oxygenation in the placenta. Injecting tracers, however, may be sensitive ethical territory. “People are very scared of doing things to pregnant women,” said Nicholas Illsley, of Hackensack University Medical Center in New Jersey, at the meeting. Another idea is to probe the mother’s bloodstream for cells and nucleic acids shed by the placenta as a window into the function of the organ. Researchers also mused about creating a “placenta on a chip” that would mimic the tissue in the lab and developing molecular sensors that could monitor the placenta throughout pregnancy. “This sounds like science fiction, but if you showed me an iPhone 20 years ago, I would have said this was science fiction,” said Yoel Sadovsky, of the Magee-Womens Research Institute in Pittsburgh, Pennsylvania, at the meeting. Attendees described a few immediate goals. One is to come up with standard definitions of a normal and abnormal placenta. Placenta morphology varies widely, and those from a healthy pregnancy can still have visible abnormalities, whereas those from sick babies often look completely normal, says systems biologist Brian Cox of the University of Toronto in Canada. Even before the NICHD meeting, the international community of placenta researchers had begun to coordinate their efforts by planning a website that will list existing placenta biobanks and help match collaborators. At a time when NICHD’s budget is flat, money could be a limiting factor for the Human Placenta Project, which Guttmacher hopes will fund its first grants in 2016 and go for a decade or more. He expects that in addition to setting aside new money for the project, NICHD may give extra weight to high-quality grant applications focusing on the placenta. NICHD’s own contribution may be only “in the millions” of dollars, Guttmacher says. But he says eight other NIH institutes have expressed interest in contributing, as has the March of Dimes, an organization long focused on maternal and infant health. At long last, a throwaway organ may get the attention it deserves. ■ 6 JUNE 2014 • VOL 344 ISSUE 6188

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The placenta’s complex vasculature (blue) sustains a fetus through its umbilical cord (white).

Reproductive biology. Gearing up for a closer look at the human placenta.

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