Systems Approaches to Identify Metabolite Signatures in Placental Development

The human placenta is essential for successful pregnancy as it performs critical functions such as transfer of nutrients and oxygen to the fetus, removing harmful waste products, and providing mechanical, hormonal and immune support. Alterations to placental function can have profound impacts on the health of the developing fetus and the outcome of the pregnancy. In this study, we analyzed transcriptomic data of 200 term placentae and identified expression levels for metabolic genes. We used the most comprehensive human metabolic reconstruction, Recon 3D, and integrated transcriptomics data with the model to make it placenta-specific. The draft reconstruction of placenta consists of about 5525 reactions, more than 5500 metabolites and captures about 80% reactions in subsystems such as Vitamin K metabolism, cholesterol metabolism, citric acid cycle, chondroitin synthesis, nucleotide metabolism and glycerophospholipid metabolism compared with Recon 3D model. This is the first in silico metabolic network of the human placenta and will serve as a platform to integrate longitudinal transcriptomic and metabolomic data throughout pregnancy. We have also developed a pipeline to integrate a placental transcriptional regulatory network with this metabolic network, thus making it possible to predict transcription factors that regulate metabolic changes in placenta. Placenta metabolic reconstruction provides insights into normal placental development and can also be used to predict metabolic signatures in pregnancy complications. We aim to develop a predictive methodology that combines information from various omics measurements with metabolic reconstruction that can be used to predict a metabolic trajectory across pregnancy.