Genetic-level understanding for earlier preeclampsia detection
Researchers estimate between three and five percent of pregnant women develop preeclampsia in the United States each year. The pregnancy complication is typically diagnosed after 20 weeks of pregnancy, and if left untreated could lead to the death of the mother or child. Treatment often involves inducing early delivery, which results in premature birth.
Once thought to be caused by a toxin in the blood, healthcare providers now understand the pregnancy disorder is much more complex. This new understanding has encouraged scientists to research new factors that could contribute to the development of the disease.
Geetu Tuteja investigates the genetic architecture underlying disorders in placenta development. She hopes that a better understanding of the genetic mechanisms will help clinical researchers develop early detection and prevention methods for placental disorders, such as preeclampsia.
Tuteja is an assistant professor in the Department of Genetics, Development and Cell Biology and a Gregory L. and Kathleen C. Geoffroy Faculty Fellow. She studies “trophoblast invasion,” a process that occurs in early development of a fetus. In trophoblast invasion, “invading” is a good thing. The fetal cells of the placenta migrate into the maternal part to enable blood to flow from the mother to the fetus.
“Our lab is interested in the mechanisms of the invasion,” Tuteja said. “We look at what genes are expressed and what DNA sequences regulate those genes during invasion. When these genes are not regulated properly, the fetal cells might not invade as much as they should, or might invade more than they should.”
If trophoblasts do not invade enough, it can lead to blood-flow problems between mother and fetus, which can lead to preeclampsia or to intra-uterine growth restriction (when the fetus does not grow at a normal rate in the womb). At the other extreme, trophoblast over-invasion can cause the placenta to attach too deeply to the mother, resulting in hemorrhaging, which must be treated by hysterectomy.
Tuteja’s lab, which combines techniques from genomics, computational biology, and molecular biology, uses mouse placenta to gain a better understanding of the human placenta. After purifying millions of RNA or regulatory DNA fragments from the placenta, the lab uses next-generation sequencing technology to sequence them. Her team then uses computational analysis to interpret the massive amount of data produced by the sequencing.
“These approaches allow us to identify important parts of the genome including the genes that are expressed during trophoblast invasion, as well as the genomic sequences that could activate genes regulating trophoblast invasion,” she said.
Her past research has identified thousands of genomic regions that are highly active during trophoblast invasion in a mouse. She predicts that a group of at least three proteins bind together to many of these genomic regions to regulate trophoblast invasion genes. Now, her team is trying to identify specific genomic regions that directly affect trophoblast invasion if they are mutated.
Her research could have a broad impact on society and the health of pregnant women across the globe.
“The symptoms of preeclampsia do not typically manifest until the middle of the second trimester, even though abnormalities that can lead to it occur in the first trimester,” Tuteja said. “By studying early placental development, we hope that our research will eventually lead to early detection and prevention of certain pregnancy disorders, as well as other problems that arise as a result of abnormal placental development.”