Longitudinal profiling of the pregnancy plasma proteome through organic solvent precipitation and nano LC-MS/MS

Proteins secreted from maternal, fetal, and placental tissue are vital for processes like placental development, immunotolerance, and fetal growth, and are associated with pregnancy complications, necessitating predictive biomarkers. In this study, we introduce an acetonitrile-based precipitation coupled with solid-phase extraction that addresses limitations of current low throughput blood-based biomarker discovery workflows. Our method is efficient and cost-effective, and identified 433 protein groups, showing specific tissue associations and enrichment in reproductive tissues such as the placenta, breast, and endometrium. Significant alterations in proteins related to hormonal regulation, immune modulation, and placental development throughout gestation were observed. This approach offers comprehensive insights into the circulating pregnancy proteome, but also provides a scalable solution for larger studies for biomarker discovery in the context of pregnancy complications. TOC