Understanding Childbirth Through a Single-Cell Atlas of the Placenta
Posted on by Dr. Monica M. Bertagnolli
While every birth story is unique, several parents might agree that going into labor is an unpredictable process. Although most pregnancies last about 40 weeks, about one in every 10 infants in the United States. are born before the 37th week of pregnancy, when their brain, lungs, and liver are still developing.1 Some pregnancies also end in an unplanned emergency caesarean delivery after labor fails to progress, for reasons that are largely unknown. Gaining a better understanding of what happens during healthy labor at term may help to elucidate why labor doesn’t proceed normally in some cases.
In a recent development, NIH scientists and their colleagues reported some fascinating new findings that can one day give healthcare providers the tools to better understand and perhaps even predict labor.2 The research team produced an atlas showing the patterns of gene activity that take place in various cell types during labor. To create the atlas, they examined tissues from the placentas of 18 patients not in labor who underwent caesarean delivery and 24 patients in labor. The researchers also analyzed blood samples from another cohort of more than 250 people who delivered at various timepoints. This remarkable study, published in Science Translational Medicine, is the first to analyze gene activity at the single-cell level to better understand the communication that occurs between maternal and fetal cells and tissues during labor.
The placenta is an essential organ for bringing nutrients and oxygen to a growing fetus. It also removes waste, provides immune protection, and supports fetal development. The placenta participates in the process of normal labor at term and preterm labor. Problems with the placenta can lead to several issues, including preterm birth. To create the placental atlas, the study team used an approach called single-cell RNA sequencing. Messenger RNA molecules transcribed or copied from DNA serve as templates for proteins, including those that send important signals between tissues. By sequencing RNAs at the single-cell level, it’s possible to examine gene activity and signaling patterns in several thousands of individual cells at once. This method allows scientists to capture and describe in detail the activities within individual cell types along with interactions among cells of different types and in immune or other key signaling pathways.
Using this approach, the researchers found that cells in the chorioamniotic membranes, which surround the fetus and rupture as part of the labor and delivery process, showed the greatest changes. They also found cells in the mother and fetus that were especially active in generating inflammatory signals. They note that these findings are consistent with previous research showing that inflammation plays an important role in sustaining labor.
Gene activity patterns and changes in the placenta can only be studied after the placenta is delivered. However, it might be ideal if these changes can be identified in the bloodstream of mothers earlier in pregnancy—before labor—so that health care providers can intervene if necessary. The recent study showed that this was possible: Certain gene activity patterns observed in placental cells during labor can be detected in blood tests of women earlier in pregnancy who might later go on to have a preterm birth. The authors note that more research is needed to validate these findings before they can be used as a clinical tool.
Overall, these findings offer important insight into the underlying biology that normally facilitates healthy labor and delivery. They also offer preliminary proof-of-concept evidence that placental biomarkers present in the bloodstream during pregnancy may help to identify pregnancies at increased risk for preterm birth. While much more work and larger studies are needed, these findings suggest that it may one day be possible to identify those at risk for a difficult or untimely labor, when there is still opportunity to intervene.
The research was conducted by the Pregnancy Research Branch part of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), and led by Roberto Romero, M.D., D.Med.Sci., NICHD; Nardhy Gomez-Lopez, Ph.D., Washington University School of Medicine in St. Louis; and Roger Pique-Regi, Ph.D., Wayne State University, Detroit.
 Preterm Birth. CDC.
 Garcia-Flores V, et al., Deciphering maternal-fetal crosstalk in the human placenta during parturition using single-cell RNA sequencing. Science Translational Medicine DOI: 10.1126/scitranslmed.adh8335 (2024).
NIH Support: Eunice Kennedy Shriver National Institute of Child Health and Human Development
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