This week we profile a recent publication in Epigenetics & Chromatin from Chaini Konwar (third from right) and Dr. Wendy Robinson (left) at the BC Children’s Hospital Research Institute and UBC.
Can you provide a brief overview of your lab’s current research focus?
Our lab focuses on how our genes, in combination with other risk factors, influence placental and fetal development. Establishing a pregnancy, maintaining it, and supporting fetal growth involves a complex interplay between maternal and fetal signals, largely mediated by the placenta. Early exposures (nutrition, stress and disease) are increasingly appreciated in playing a role in modifying gene expression in development and affecting fetal growth and neonatal outcomes. However, both maternal and placental-fetal genetic variation likely mediates a substantial portion of these influences and their effect on the placenta. Our studies are focused on understanding 1) normal placental genetic and epigenetic variation including DNA methylation changes associated with sex and gestational age; 2) what the placenta can tell us about fetal health; 3) the role of pregnancy associated inflammation and development. Ultimately we hope that this work will lead to improved early diagnosis of pregnancy complications and approaches to reduce their incidence.
What is the significance of the findings in this publication?
Each year, about 1 in 10 babies worldwide are born before the pregnancy has reached full term. Babies born too early are at an increased risk of life-threatening infections, long-term developmental delay and poor health outcomes. One of the major causes of preterm birth is inflammation of the placenta and its membranes. Roughly 25-40% of preterm births are caused by this type of inflammation, however, diagnosis is generally not made prior to delivery.
Using samples of tissue collected from donated placentas from preterm births with and without inflammation, we examined DNA methylation, a chemical mark on DNA that is associated with how genes are turned on and off in the cell. We were able to identify unique DNA methylation changes in the placenta associated with inflammation in preterm birth pregnancies. These DNA methylation changes could reflect alterations in immune cell numbers during placental inflammation and/or may represent an immune response specific to the placenta. Interestingly, this is the first study to investigate genome-wide DNA methylation alterations in inflammation-associated placentas.
Because placental DNA, RNA, and proteins are released into maternal blood during pregnancy, changes in gene regulation observed in the placenta can be associated with altered levels of corresponding DNA/RNA or proteins in maternal blood. This research therefore identifies candidates for further exploration to predict which pregnancies are most in need of careful monitoring and intervention. In addition, by identifying placental changes associated with preterm-birth, we can start to explore how different risk factors might affect these biomarkers of placental inflammation.
What are the next steps for this research?
Our next goal is to better understand the genetic and environmental risk factors that predispose placentas to inflammation leading to preterm birth. In particular we are interested in how genetic variants affecting immune response might make some pregnancies more susceptible to inflammation and/or infection. We are also interested in how stress affects placental DNA methylation and how that might the affect risk for placental inflammation. As pregnancies with a male fetus are more vulnerable to inflammation, we are also interested in understanding sex- differences in placental gene regulation and expression.
This research was funded by:
Our work was funded through a Canadian Institutes of Health Research (CIHR) grant. In addition salary and other support is received from the BC Children’s Health Research Institute.
