Fetal growth restriction (FGR) is a serious global disease, affecting up to 10% of all pregnancies. It is one of the main reasons for disability, illness and death in newborn babies, and increases their risk of development delays as well as their future risk of heart disease, hypertension, type 2 diabetes and stroke in adult life. There is currently no cure for FGR and we do not have effective markers that can be used to screen or predict the likelihood of developing FGR in pregnancy.
A new study by researchers from the MRC Weatherall Institute of Molecular Medicine (MRC WIMM), University of Oxford and the Broad Institute of MIT and Harvard published in Nature Communications, demonstrates how certain combinations of parental and fetal immune genes lead to development of FGR in pregnancy.
This elegant study conducted at the Oxford Centre for Neuroinflammation led by Professor Lars Fugger at the MRC Human Immunology Unit in Oxford and in collaboration with Prof. Aviv Regev at the Broad Institute of MIT and Harvard, demonstrates how a discrete interaction between two immune genes leads to cellular crosstalk and transcriptional changes in a range of cell types at the maternal-fetal interface.
Dr Gurman Kaur (based at the MRC WIMM, Oxford and the Broad Institute of MIT and Harvard) in collaboration with Dr Caroline Porter (Broad Institute of MIT and Harvard) developed and employed a novel model system to show that products of two risk genes, the inhibitory KIR2DL1 receptor expressed on maternal uterine natural killer cells, and paternally-derived HLA-C*0501, an HLA-C group 2 allotype, expressed on fetal trophoblast cells, leads to FGR. The team employed cutting-edge technologies including single-cell technologies and micro-computated tomography imaging, and were able to show that the interaction between these genes leads to changes in the uterine spiral arteries that develop in pregnancy, providing a higher resistance to fetal blood flow in FGR.
The research provides a mechanistic understanding of FGR as a complex multicellular disease, and highlights gene candidates which have the potential to be modulated for therapeutic intervention, and improve clinical outcomes for both the mother and the baby.
Read the paper at Nature Communications.