York research presents novel evidence on development of preeclampsia

A specific microRNA is identified for the first time as a key contributor to the development of preeclampsia, a complication of pregnancy, in a study by York University.

The study provides evidence that the microRNA “miR-218-5p” promotes the invasion of placental cells and induces the remodelling of blood vessels in the uterus. The research also shows that miR-218-5p levels are lower in placentas from preeclamptic pregnancies, and that dysregulation of that microRNA may contribute to the development of preeclampsia.

An image of the co-culture system used in the research. It shows human umbilical vein endothelial cells cultured with trophoblasts (placena cells)

The study’s first author is Jelena Brkic, a former PhD student and postdoctoral Fellow working under Chun Peng, York’s Research Chair in Women’s Reproductive Health and biology professor. The research team collaborated with researchers in several hospitals, in particular with Stephen Lye’s research team at the Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital.

The causes of preeclampsia are not fully understood, but it is known that abnormal placental development – in particular, the insufficient invasion of placental cells into the uterus to carry out the remodelling of the uterine blood vessels – is a major contributing factor. Deficiency in this major event of early pregnancy compromises the volume and flow of blood to the developing fetus.

Preeclampsia not only has adverse effects on the health of the mother and fetus during pregnancy, but can have lifelong negative impacts on cardiovascular health. It is typically characterized by high blood pressure and indications of damage to liver, kidneys or other organs, and can be fatal.

It is the leading direct cause of maternal/neonatal morbidity and mortality, and currently the only treatment is delivery of placenta and baby, often preterm.

“Our findings strongly suggest that miR-218-5p plays important roles in maintaining healthy pregnancy and its abnormal expression may contribute to the development of preeclampsia,” said Peng.

“The possibility of using miR-218-5p as a biomarker of preeclampsia, and possibly other disorders of pregnancy, is something we plan to investigate further,” said Brkic. “This study also highlights that miR-218-5p is an excellent candidate for miRNA-based therapeutics with respect to exploration of early preeclampsia intervention.”

The study, “MicroRNA-218-5p Promotes Endovascular Trophoblast Differentiation and Spiral Artery Remodeling,” is published in the journal Molecular Therapy.