Serum Proteomic Signatures in Umbilical Cord Blood of Preterm Neonates Delivered by Women with Gestational Diabetes

Abstract

Background

Women who develop diabetes during pregnancy are at higher risk of preterm birth. Here, we identified differentially expressed proteins (DEPs) in the serum of umbilical cord blood samples obtained from preterm neonates delivered by women with gestational diabetes to provide therapeutic targets for clinical drug development.

Materials and Methods

Umbilical cord blood was collected after delivery of preterm neonates by women with gestational diabetes and after delivery of healthy neonates by women without diabetes. DEPs in the serum samples were identified using liquid chromatography–tandem mass spectrometry. Gene Ontology (GO), cluster analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to determine the biological functions associated with these DEPs. Enzyme linked immunosorbent assay was used to confirm the key DEPs.

Results

We found that 21 proteins were significantly upregulated, and 51 proteins were significantly downregulated in 72 DEPs in serum samples. GO analyses showed that the DEPs were mainly associated with the GO terms cellular process, biological regulation, cellular anatomical entity, and binding. KEGG signaling pathway analysis indicated that most of the upregulated DEPs were associated with the complement and coagulation cascades, Staphylococcus aureus infection, pertussis, HIF-1 signaling pathway and PPAR signaling pathway and that most of the downregulated DEPs were associated with the complement and coagulation cascades, dilated cardiomyopathy, pathways in cancer, Chagas disease, and hypertrophic cardiomyopathy. The results of KEGG pathway annotation and enrichment analyses indicated that changes in the complement and coagulation cascades may be importantly associated with preterm delivery of neonates by women with gestational diabetes. The key DEPs were confirmed by enzyme linked immunosorbent assay.

Conclusion

Our proteomics and bioinformatics analyses identified several key proteins and the complement and coagulation cascades pathway that warrant further investigation as potential novel therapeutic targets in preterm delivery among women with gestational diabetes.

Keywords:

• label-free LC-MS/MS
• proteomics
• gestational diabetes
• preterm birth
• complement and coagulation cascades

Acknowledgments

We would like to express our gratitude to Yunxia Lu, Ph.D. and the technicians in the Comprehensive Experiment Center of Basic Medical Sciences, Anhui Medical University, for facility support, and the Center for Scientific Research of Anhui Medical University for valuable help with our study.

Disclosure

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Additional information

Funding

This work was supported by grants from the Key Project of Medical Application Research of He-fei Municipal Health Commission (grant No. Hwk2021zd016) and the National College Student Innovation and Entrepreneurship Training Program (Grant No. 202110366018X).