Study provides new explanation for why placenta may not properly separate at birth, putting mother and newborn at risk

Feb. 2, 2024
UCLA researchers identify genetic and cellular changes underlying placenta accreta spectrum disorder.

A new study led by researchers at UCLA may change the way clinicians and scientists understand, diagnose and treat placenta accreta spectrum disorder, a serious condition in which the placenta fails to separate from the uterus at birth, jeopardizing the life and health of both mother and baby.

Researchers previously believed that certain overly invasive placental cells, called trophoblasts, were responsible for keeping the connection intact. But this new research, which identifies genetic and cellular changes within single cells where the placenta and uterus join, shifts the focus to how the structural support of tissues, and the blood vessels of the uterus, can cause a “loss of normal boundary limits” between the placenta and the uterus.

“We utilized two new techniques in single-cell analysis to create an atlas of cells involved in placenta accreta to better understand this increasingly prevalent disorder that can have devastating implications for maternal and neonatal health,” said Dr. Yalda Afshar, a maternal-fetal medicine specialist and researcher at the  David Geffen School of Medicine at UCLA, and the first and corresponding author of an article describing the findings in the American Journal of Obstetrics & Gynecology.

“This work revealed a subset of genes differentially expressed in placenta accreta spectrum disorder, which provides the basis for the ‘permissive environment’ for the placenta to attach to the uterine lining,” said Dr. Deborah Krakow, a maternal-fetal medicine specialist and researcher, chair of the Department of Obstetrics and Gynecology at the David Geffen School of Medicine at UCLA, and the paper’s senior author.

The research showed that the decidua, the layer of the uterine lining that forms during pregnancy, and blood vessels, are sending different signals to the placenta when a pregnant person has placenta accreta. Normally, the placenta – the temporary organ that provides support for a fetus – is shed after birth. In placenta accreta, it is stuck on too tight, which becomes the reason for many of the maternal complications of placenta accreta.

For this study, the research team performed multiple placental biopsies on 12 placentas – six with PAS disorder and six controls – conducting single-cell RNA analysis on 31,406 individual cells. The researchers also applied spatial transcriptomics to 36 regions of interest – 12 in PAS-adherent, 12 in PAS-nonadherent, and 12 in controls. Spatial transcriptomics allow researchers to precisely measure and map the gene activity within a single tissue sample.

UCLA release