Preeclampsia is a serious high blood pressure condition that affects about 1 in 10 pregnancies worldwide and can lead to severe complications for moms and babies. It can also increase long-term health risks beyond pregnancy. Even though preeclampsia affects so many families, scientists are still trying to understand exactly what causes it and how to treat it.

A new study has uncovered an important clue in the placenta, the organ that helps a baby get oxygen and nutrients during pregnancy.

Researchers at the University of Michigan found that a gene called VGLL3 (vestigial-like family member 3) is more active than normal in placentas affected by preeclampsia. This gene may play a bigger role in the disease than scientists previously knew.

The team discovered that too much VGLL3 can cause three major problems:

• It affects how the placenta grows: It can stop important placental cells, called trophoblasts, from developing the way they should. These cells help the placenta grow and work properly.
• It affects blood vessels: It can harm the cells that line blood vessels, making it harder for blood to flow properly.
• It affects the immune system: It can make the body's immune system too active, leading to harmful inflammation.

Together, these problems can contribute to high blood pressure during pregnancy, intrauterine growth restriction (IUGR), and even the loss of a baby.

Researchers also found that VGLL3 acts before some of the changes linked to preeclampsia, including before the release of a protein called sFLT1. This protein is already known to be an important sign of preeclampsia.

One of the most exciting discoveries was that blocking VGLL3 helped protect against preeclampsia. When researchers removed VGLL3 from placentas in mice or used a treatment to block it in human placental samples, they saw improvements in disease markers.

This research gives scientists a new way to understand how preeclampsia develops and points to VGLL3 as a possible target for future treatments. The study also showed a biological connection between VGLL3, preeclampsia, autoimmune diseases, and the age when a lady gets her first period. Further research may help scientists better understand why some women are more likely to develop preeclampsia.

Take-home message: Although more research is needed, this study brings new hope for VGLL3 and its associated signaling network as promising new therapeutic targets for preeclampsia.

Citation: Plazyo O, Chopp LB, Peela R, Young K, Zhang H, Bogle R, Hesson A, Langen ES, Bergin IL, Syu LJ, Erba J, Kirma J, Dey P, Zhang L, Sarkar MK, Swindell WR, Gallagher KA, Ward NL, Singer K, Kahlenberg JM, Billi AC, Dlugosz AA, Ganesh SK, Tsoi LC, Gudjonsson JE. Defective Trophoblast Differentiation, Endothelial Dysfunction, and Immune Dysregulation in Preeclampsia Coalesce on a Placental VGLL3-Centered Gene Network. Circulation. 2026 Jun 2;153(22):1743-1760. doi: 10.1161/CIRCULATIONAHA.125.076218. Epub 2026 Apr 9. PMID: 41953989; PMCID: PMC13120743. Defective Trophoblast Differentiation, Endothelial Dysfunction, and Immune Dysregulation in Preeclampsia Coalesce on a Placental VGLL3-Centered Gene Network - PubMed