This article has been reviewed according to Science X's editorial process and policies. Editors have highlighted the following attributes while ensuring the content's credibility: Exposure to toxic metals like cadmium has been associated with adverse pregnancy outcomes such as miscarriage, preterm birth and low birth weight. Because these effects are difficult and ethically challenging to study directly in pregnant women, how such exposures affect pregnancy has remained poorly understood.
The placenta-on-a-chip model developed by Dan Huh, J. Peter Skirkanich professor in bioengineering, and colleagues at Penn Engineering offers a way to investigate these questions using living human cells. In a study published in Nature Biomedical Engineering, the team led by Huh, together with collaborators at Princeton, Sogang University in Seoul, Korea, and Rutgers University, used the bioengineered model to examine how cadmium, a toxic metal found in food, drinking water and tobacco smoke, affects the placenta's ability to support a developing fetus.
The group's experiments revealed that cadmium can impair the placenta even at relatively low exposure levels that do not kill cells. The researchers also identified a protein that helps protect placental tissue, along with metabolic changes that could provide clues to exposure-related damage. In the placenta, maternal and fetal blood circulate in separate compartments and exchange nutrients and other substances across a thin layer of tissue.
Huh and his collaborators developed a microfluidic device that recreates key features of this maternal–fetal interface. The device is built with human placental cells isolated from donated placentas. On one side, a layer of these cells is exposed to flowing fluid that simulates maternal blood.
On the other, a three-dimensional tissue structure contains a network of fetal blood vessels embedded in a hydrogel scaffold. The model also incorporates oxygen conditions that more closely reflect those inside the placenta than conventional cell culture systems. Researchers can introduce additional cell types, including placental immune cells, to investigate more complex biological responses.
Huh's earlier placenta-on-a-chip research focused on how drugs cross the placental barrier. "Our new work expands the original capabilities of the technology and allows us to emulate the human maternal–fetal interface with greater fidelity and study the effect of environmental toxins under more realistic conditions," says Huh. "We can now ask not only whether cadmium crosses the barrier but also how it affects the placenta's ability to perform its key physiological functions." The researchers exposed the engineered tissue to different concentrations of cadmium and measured its effects on cell viability, barrier integrity, hormone production and nutrient transfer.
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