Pre-eclampsia is a life-threatening pregnancy complication that can strike suddenly, endangering both mother and child. Despite affecting roughly one in twenty pregnancies worldwide, clinicians have long lacked a reliable method to predict its onset.
Now, a breakthrough study published in Genome Biology may change that. Led by Dr Manvendra Singh (INEM, and Institut Imagine) alongside collaborators from the Max Delbrück Center, Cornell University and the University of Bath, researchers have uncovered ‘hidden’ biological signals that could serve as an early-warning system.
Their work reveals previously unknown processes that drive healthy and unhealthy placental development and identifies two powerful early markers that may allow pre-eclampsia to be detected weeks before symptoms appear.
“Pre-eclampsia is both remarkably common (around 5 per cent of pregnancies) and potentially lethal,” says Professor Laurence Hurst at the University of Bath's Department of Life Sciences and Milner Centre for Evolution, a co-corresponding author. “It is the second most common killer of mothers globally, making it both an evolutionary conundrum and a serious maternal and neonate health problem.
“Unfortunately, pre-eclampsia is often recognised too late – when a pregnant woman’s blood pressure is already dangerously very high.”
Ancient viral DNA acts as molecular switch
By tracking how certain genes are switched on in the placenta, the researchers discovered that small regulatory regions in our retroviral DNA (genetic remnants of ancient viruses passed down from our ancestors) play a critical role in determining whether the placenta develops normally.
When these molecular switches malfunction, the placenta fails to form properly, a hallmark of pre-eclampsia. Interestingly, the team found that these disruptions leave measurable traces in the mother’s blood early in pregnancy, offering the potential for a non-invasive screening test.
“This work shows that an ancient viral sequence can act like a manual for a placental gene,” explains Dr Manvendra Singh, lead author of the study and former postdoc at the Max Delbrück Center and who is now Group Leader at the INEM and Institut Imagine. “By mapping the regulatory region and testing it functionally, we have now connected genome evolution to a concrete disease mechanism – and to the possibility of earlier detection.”
Specifically, the study reveals that PSG9, a specific pregnancy protein, is regulated by the two fragments of ancient viral remnants in our DNA (LTR8B and MER65). When this regulation malfunctions, it triggers a cascade of events linked to Early-Onset Pre-eclampsia (EO-PE), offering a precise new target for blood-based screening.
Potential marker for earlier screening
The findings open a new window into how pre-eclampsia begins and point toward tools that could transform maternal care: earlier screening, more accurate risk prediction, and the possibility of future treatments targeting these newly uncovered procedures.
“What made this discovery powerful was being able to move from prediction to direct functional tests,” says Professor Zsuzsanna Izsvák, who led the experimental work at the Max Delbrück Center and is a corresponding author on the paper. “The placenta depends on precisely tuned gene regulation, and retroviral elements sit at the centre of that tuning.”
This work brings us one step closer to making the invisible visible, turning a silent, life-threatening disorder into something we can finally detect, understand, and one day prevent.