Researchers from a global collaboration have identified patterns of gene expression associated with a healthy pregnancy using circulating RNA.
Pregnancy and associated complications
Conception to delivery is a rapid stage of growth and development that requires dramatic alterations in maternal physiology that are currently poorly understood. Research into human pregnancy is limited due to ethical constraints and current conventional animal models are of limited value.
Pre-eclampsia is a condition that complicates up to 1 in 12 pregnancies. It is characterised by maternal endothelial dysfunction and is associated with new-onset maternal hypertension. As a result, it is a significant cause of maternal morbidity and is associated with a higher lifetime risk of cardiovascular disease. Unfortunately, the ability to assess underlying conditions before clinical presentation is difficult.
RNA profiles of pregnancy health
In a recent study, published in Nature, researchers gathered the largest and most diverse dataset of maternal transcriptomes to date to identify patterns of pregnancy progression. More specifically, the samples were obtained from 1,840 pregnancies for women of multiple ethnicities, nationalities, geographic locations and socioeconomic contexts. These pregnancies also covered a range of gestational ages. The pre-eclampsia data included 524 samples (72 cases and 452 non-cases) from two diverse independent cohorts.
The team analysed maternal, foetal and placental RNA circulating in the mother’s blood during pregnancy. From this, they identified patterns of gene expression associated with a healthy pregnancy. They confirmed that their activity mirrored the physiological changes expected at different time points, such as foetal heart development. The technique performed equally as well or better than state-of-the-art methods.
They also correctly predicted a risk of preeclampsia in 75% of cases and a risk of preterm birth at a similar rate. The plasma cell-free RNA (cfRNA) signatures for pre-eclampsia were independent of clinical factors, such as maternal age, body mass index and race. They were also found to contain gene features linked to the biological processes that have been implicated in the underlying pathophysiology of the condition.
The researchers hope that cfDNA sequencing could improve preventative care for maternal conditions like preeclampsia. Analysing RNA profiles could also help researchers develop new therapeutic strategies and better select candidates for clinical trials.
Senior author, Thomas McElrath, said:
“Looking at the progression of genes expressed in the mother and baby during pregnancy offers an entirely new way of characterising their health that hasn’t been available up until now.
Early detection of disease using this approach will provide us with the distinct possibility of therapeutically addressing some of these conditions.”
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