Study discovers new therapeutic targets for severe preeclampsia

Unusual behavior in the cells of mothers and babies with preeclampsia may provide new therapeutic targets for the condition, finds a new UCL-led study.

Preeclampsia is a leading cause of maternal and fetal mortality, affecting 2 to 4% of pregnancies globally. The condition causes the mother's blood pressure to become too high, which can affect blood flow to the baby and cause symptoms like swelling, headaches, blurred vision and pain under the ribs.

If left untreated, it can harm the mother's health, slow the baby's growth and, in severe cases, be a threat to life. However, there is currently no cure.

Now, in a new study published in Science Advances, scientists from UCL and University College London Hospitals (UCLH), have discovered that a combination of stressed placental cells, poorly functioning blood vessels, and an overactive immune response all contribute to the condition.

Previous research has only focused on the placenta (an organ developed by the mother during pregnancy, that helps support a baby's growth) and not on the tissues surrounding it.

The researchers hope that their findings will provide new therapeutic targets for preeclampsia and a potential way to treat those with the condition.

Senior author, Professor Sara Hillman (UCL EGA Institute for Women's Health): "We studied individual cells from both the mother and the baby to see how their activity changes in healthy pregnancies compared with preeclampsia.

"This helped us to confirm some changes already suspected in the condition and also discover new ones."

For their research, the team studied 20 pregnant women – 10 of whom had severe preeclampsia and 10 without – who were recruited at UCLH.

They used genomic testing to investigate the individual cells in the placenta and other tissues (myometrium and chorioamniotic membranes) where cells from the developing baby and mother meet.

The team then compared these cells to those from healthy and preeclamptic pregnancies at different gestational ages.

They did this by using novel technology that helped them to read the genetic information of thousands of individual cells at a time, to understand what each cell was doing and where they sit in a tissue, to build up a detailed picture of the pregnancy.

They found that in preeclamptic pregnancies where babies were born premature (before 37 weeks) during the third trimester, the cells in the placenta showed signs of stress and low oxygen and didn't use energy in the normal way.

Additionally, they found that some cells responsible for reshaping the mother's blood vessels weren't working properly, which may affect blood flow to the baby.

Crucially, there were also signs of an overactive immune response – not just in the placenta but nearby tissues and even in the mother's blood. This, along with other stress molecules released by the placenta, helps to explain why preeclampsia affects the whole body and can become a serious condition.

The researchers hope that these findings will help to finally find treatments for the condition and even save lives.

Co-lead author, Dr Yara Sanchez Corrales (UCL Great Ormond Street Institute of Child Health) said: "These findings point to specific biological processes that could be targeted with treatments. Acting early in pregnancy, especially in more severe early-onset cases, could help improve outcomes and reduce the high risks associated with severe preeclampsia.

"We hope that our findings may set us on the path to reducing premature births and fatalities associated with preeclampsia. "

Co-lead Mr Theodoros Xenakis (UCL Great Ormond Street Institute of Child Health), said: "Future studies may provide an even clearer picture of the biological changes linked to the disease by including more participants and using even more precise methods."

Both Dr Sanchez Corrales and Mr Xenakis are in Professor Sergi Castellano's lab at the UCL Great Ormond Street Institute of Child Health.

The research was funded by the Medical Research Council (MRC) and the NIHR GOSH Biomedical Research Centre (BRC). The research was also supported by the UCLH BRC.

Study limitations

The researchers were limited by the small number of donors when looking at very subtle gene changes in some rare cell types. Future studies that include more people and use even higher-resolution methods may uncover additional, more detailed biological changes linked to the disease.