We now live in exciting times for placenta research. Technological innovations in recent years are enabling unprecedented acquisition of data at an increasingly affordable price. We are assessing placental differentiation, growth and function across gestation in health and disease using multi-omics and reflecting those in matched maternal blood samples obtained at the same time as placenta is accessed or in serial samples across gestation. To date we have undertaken miR-seq, RNA-seq, Illumina DNA EPIC Array analyses in placenta, and miR-seq in maternal plasma and Illumina DNA EPIC arrays in maternal circulating leukocytes for 288 pregnancies. The volume of data is at the terabyte scale. For example, three omics in 96 placenta samples from 6-23+6 weeks of gestation obtained with consent from elective terminations of pregnancy result in about 500GB of data. Add to that two omics in maternal blood and data from another 192 preterm and term pregnancies and we have a dataset that requires High Performance Computing, multiple bioinformaticians and a biostatistician to enable integration and accurate bio-inference of these data with reference to clinical and lifestyle data and pregnancy and birth outcomes.
Three-omic analysis of the first 96 placenta samples shows that differential expression of coding and non-coding RNAs occurs simultaneously with that of micro RNAs and DNA methylation demonstrating epigenetic regulation of expression. These are changing dynamically week by week, trimester by trimester, before and after maternal blood begins to flow into the placenta at 10 weeks’ gestation, in a fetal sex specific fashion, and in response to environmental exposures such as maternal obesity and smoking. In time, non-invasive screening of placental, hence fetal, health in real time will become a reality and may be used to identify and monitor pregnancies at risk.
Supported by NIH NICHD R01 HD089685-01 Maternal molecular profiles reflect placental function and development across gestation PI Roberts