Background: Preeclampsia (PE) is a pregnancy specific condition characterized by hypertension, inflammation and proteinuria, and a leading cause of maternal-fetal morbidity and mortality [1]. There are several preclinical models of PE, such as the immunological model, which mimics the proteinuria and hypertensive features of PE [2]. However, the model’s capacity to recapitulate other components of the PE phenotype has not been fully investigated. As such, global methods, such as proteomics, can be used to capture a holistic picture of these pathophysiological characteristics to better inform future studies into the disease. Methods: Placenta from control and PE rats (n=6) were collected. Protein was extracted and subject to a previously described filter-aided sample preparation, digested, acidified and desalted. 1ng of peptide was loaded onto an Orbitrap HPLC-MS/MS in duplicate and run using a data dependent acquisition method. The raw files were uploaded to MaxQuant and outputs were processed using Perseus and G-profiler for statistical analyses and data visualization. Results: Over 3000 proteins were identified, 327 of which were differentially expressed between the control and PE samples (p < 0.05). Functional enrichment analysis demonstrated that commonly implicated pathways in PE were elevated in this rat model, including inflammation, apoptosis, oxidative stress and hypoxia. Interestingly, endoplasmic reticulum stress, commonly identified in PE patients, was most significantly affected. Conclusion: Pathway enrichment analysis provides us with a mechanistic insight into the biological pathways affected within the immunological model of PE and allows us to further characterize phenotypic changes; thereby providing a better understanding of the model's benefits and limitations.
[1] August P., Sibai B.M. Preeclampsia: Clinical Features and Diagnosis. Up-To-Date. https://www.uptodate.com/contents/preeclampsia-clinical-features-and-diagnosis. (2022) Accessed September 2 2022.
[2] Gatford K., Andraweera P., Roberts C., Care A. Animal Models of Preeclampsia. Hypertension. 1363-1381, 75(6) (2020).
