Disentangling maternal pregnancy and fetal-specific plasma signatures through integrated proteomics and site-specific N-glycoproteomics

Abstract

During pregnancy, mother and fetus co-exist albeit as two physiologically distinct individuals, connected through the placenta and the umbilical cord. This connection allows for the exchange of vital substances, while individual blood homeostasis remains intact. We hypothesized that comparing maternal and cord plasma (N-glyco)proteomes would provide insights into the biological communication and unique physiological state of each individual. As comparing only matched maternal and umbilical cord blood plasma misses a crucial identifier in determining whether observed changes are related to infancy, pregnancy or both, we designed a triad study by adding a non-pregnant women control group. This allowed us to distinguish pregnancy-specific proteins and their potentially altered N-glycosylation from those in infancy. We found that the fetus and mother have distinct proteomes, N-glycoproteoforms and alternative complement regulation. Moreover, we observed that pregnancy in women led to specific N-glycosylation changes on a select set of primarily HDL-associated and acute-phase proteins. Lastly, our data provide evidence for an early fetal development of the humoral immune system as especially fetal IgM displayed distinctive N-glycosylation signatures.