The abnormal behavior of cells in pre-eclamptic mothers and their babies could represent a new therapeutic target for the condition, new UCL-led research has found.
Preeclampsia is a leading cause of maternal and fetal death, affecting 2-4% of pregnancies worldwide. This disease causes the mother’s blood pressure to become too high, which affects blood flow to the baby and can cause symptoms such as 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 can be life-threatening. However, there is currently no cure.
Now, in a new study published in scientific progressScientists at UCL and University College London Hospital (UCLH) found that a combination of stressed placental cells, malfunctioning blood vessels and an exaggerated immune response all contribute to the condition.
Previous research focused only on the placenta, an organ that a mother develops during pregnancy to help the baby grow, and not on the tissues surrounding it.
The researchers hope their findings will provide new therapeutic targets for preeclampsia and potential ways to treat it.
Senior author Professor Sarah Hillman (UCL EGA Institute of Women’s Health): “We studied individual cells from both mother and baby and looked at how their activity changes in a healthy pregnancy compared to pre-eclampsia.
“This allowed us to confirm changes in symptoms that were already suspected and to discover new changes.”
The research team studied 20 pregnant women recruited to UCLH, 10 of whom had severe pre-eclampsia and 10 who did not.
They used genomic testing to examine individual cells in the placenta and other tissues (myometrium and chorioamniotic membrane) where cells from the developing baby and mother meet.
The researchers then compared these cells to cells from healthy and preeclamptic pregnancies at different gestational ages.
They did this using new technology that reads the genetic information of thousands of individual cells at once, helping them understand what each cell is doing and where it is located in the tissue, building a detailed picture of the pregnancy.
Researchers found that in pre-eclamptic pregnancies, where the baby is born prematurely (before 37 weeks) during the third trimester, cells within the placenta show signs of stress and hypoxia and are not expending energy in the normal way.
They also found that some of the cells responsible for remodeling the mother’s blood vessels were not working properly, potentially affecting blood flow to the baby.
Importantly, not only the placenta but also nearby tissues and even the mother’s blood showed signs of an excessive immune response. This, along with other stress molecules released by the placenta, helps explain why preeclampsia affects the entire body and can be a serious condition.
Researchers hope these discoveries will eventually help find a cure for this condition and even save lives.
Co-lead author Dr Yara Sánchez-Corrales (UCL Great Ormond Street Institute of Child Health) said: “These findings point to specific biological processes that may be targeted for treatment. Acting early in pregnancy, particularly in the more severe early-onset cases, may help improve outcomes and reduce the high risks associated with severe pre-eclampsia.”
“We hope our findings provide a pathway to reducing pre-eclampsia-related preterm births and deaths.”
Co-lead author Theodoros Xenakis, from the UCL Great Ormond Street Institute of Child Health, said: “Future studies could include more participants and use more precise methods to provide a clearer picture of the biological changes associated with the disease.”
Dr Sánchez-Corrales and Mr Xenakis are both in Professor Serge Castellano’s laboratory at UCL’s Great Ormond Street Institute of Child Health.
This research was funded by the Medical Research Council (MRC) and the NIHR GOSH Biomedical Research Center (BRC). This research was also supported by the UCLH BRC.
Research limitations
Researchers were limited by the small number of donors when studying very subtle genetic changes in some rare cell types. Future studies involving larger numbers of people and using higher-resolution techniques may reveal additional, more detailed biological changes associated with the disease.
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DOI: 10.1126/sciadv.aed8964
