Maternal Blood Test Detects Pre-Eclampsia Risk Before Symptoms Develop

A major obstacle has been identifying early molecular signals that warn of risk before symptoms appear. Researchers have now discovered that ancient viral DNA embedded in the human genome helps control a placenta-related gene that, when overexpressed, triggers key features of pre-eclampsia, pointing to a potential early biomarker for the condition.

In research led by the Max Delbrück Center (Berlin, Germany) and the University of Bath (Bath, England), the team used advanced deep-learning tools and biological assays to investigate how endogenous viral DNA fragments regulate placental gene expression. The method focused on A100 Beast, a deep-learning model created in the Mobile DNA Lab at the Max Delbrück Center.

By training the AI model to interpret DNA “like language,” researchers classified regulatory sequences across species and uncovered previously overlooked enhancers — many derived from ancient viruses. In placental genomes, the model identified a cluster of ERV3-MLT1 viral enhancers that appeared unusually active. Follow-up analyses confirmed 87 virus-derived enhancers in human placental tissue, boosting nine genes commonly dysregulated in pre-eclampsia.

Experimental work then focused on one gene in particular: EPS8L1, a previously unstudied gene expressed in trophoblasts, the early placental cells essential for implantation and placental formation. Functional studies exposed the gene’s role in disease: overexpressing EPS8L1 in placental cell cultures induced hallmark features of pre-eclampsia, including diminished trophoblast invasion, impaired blood vessel formation, and oxidative stress–related cell damage. Complete knockout of the gene caused cell death, confirming its necessity for normal placental function.

A key practical finding was that a secreted form of EPS8L1 is detectable in maternal blood, where its levels tracked with known pre-eclampsia biomarkers. The gene was consistently upregulated across all study cohorts and did not appear in other pregnancy complications, suggesting it could serve as a specific early-onset biomarker for pre-eclampsia if validated in larger clinical studies.

In addition to its diagnostic potential, the research, published in Genome Biology, highlights the deep evolutionary roots of this regulatory system. The ERV3-MLT1 viral DNA driving EPS8L1 expression originated more than 100 million years ago in a common ancestor of primates and rodents, illustrating how ancient viral infections still shape modern human biology.

“These findings connect a deep evolutionary process to a very modern clinical problem and point to a potential biomarker to detect pre-eclampsia risk before symptoms develop,” said Professor Zsuzsanna Izsvák, group leader and co-corresponding author.

Related Links:
Max Delbrück Center
University of Bath