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Placental Single-Cell Expression Atlas Points to Potential Preterm Birth Biomarkers

NEW YORK – By investigating gene expression profiles in maternal and fetal cells that interact in the process of labor and childbirth, known as parturition, a team led by US investigators has uncovered placental signatures offering clues to preterm birth risk.

"We believe this marks a significant step forward in addressing the challenges of predicting preterm birth," co-senior and co-corresponding author Nardhy Gomez-Lopez, a researcher at Washington University School of Medicine, explained in an email.

"Tracking specific placental signatures could offer biomarkers for distinct subsets of preterm birth, though this concept requires further testing," explained Gomez-Lopez, who was affiliated with the National Institutes of Health and Wayne State University when the study was performed.

As they reported in Science Translational Medicine on Wednesday, Gomez-Lopez and her colleagues relied on single-cell RNA sequencing to profile gene expression patterns in individual cells in basal plate and placental villi (BPPV) and chorioamniotic membranes (CAM) tissue samples from 24 women who delivered at term with spontaneous labor and another 18 who delivered at term without spontaneous labor.

"Labor is a complex physiological process requiring a well-orchestrated dialogue between the mother and fetus," the authors explained, noting that "the cellular contributions and communications that facilitate maternal-fetal crosstalk in labor have not been fully elucidated."

The resulting cell atlas spanned nearly three dozen immune and nonimmune cell clusters in the BPPV and CAM tissues tested, the researchers reported, providing a look at placental cells at play during parturition as well as related interactions between maternal and fetal cell types.

"[W]e discovered previously overlooked cell types, such as fetal stromal and myeloid cells, with a potential role during parturition, using single-cell RNA-seq," Gomez-Lopez said, noting that the work "also delves into intercellular communication and identifies shared features between term labor and preterm labor in the placental membranes."

The team flagged labor-related inflammatory features in maternal decidual cells and fetal stromal cells of the CAM membranes that surround the fetus until rupturing during labor, for example, along with myeloid cell types from both maternal and fetal sources in the placenta.

The authors reasoned that similar pregnancy- and labor-related gene expression profiles might turn up in maternal blood samples, since past studies have shown that extracellular vesicles and other material from the placenta can show up in circulating blood samples from pregnant women.

After identifying placental tissue-related expression signatures in published transcriptome profiles from dozens of maternal blood samples, the investigators demonstrated that maternal blood could be used to pick up shifts in gene expression related to two forms of preterm birth, which is known to increase the risk of infant death and disability.

"As a proof of concept, we detected placental signatures in maternal circulation, suggesting their potential as biomarkers for preterm birth identification," Gomez-Lopez said, though she cautioned that "further research is needed to establish their predictive value."

In particular, she and her colleagues reported that "early in gestation, labor-specific, placenta-derived signatures could be detected in the circulation of women destined to undergo spontaneous preterm birth, with either intact or pre-labor ruptured membranes."