Postpartum alterations following inflammation in rat pregnancy: a discovery proteomic analysis

in Reproduction
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  • 1 Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya, Japan
  • 2 Department of Obstetrics and Gynecology, Fujita Health University School of Medicine, Kutsukake-cho, Toyoake, Japan
  • 3 Queen’s Cardiopulmonary Unit, Translational Institute of Medicine (TIME), Department of Medicine, Queen’s University, Kingston, Ontario, Canada
  • 4 Department of Biomedical and Molecular Sciences, Queen’s University, Kingston, Ontario, Canada

Correspondence should be addressed to C H Graham; Email: grahamc@queensu.ca
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Women with a history of preeclampsia have an increased risk of subsequent cardiovascular and metabolic disease. While aberrant inflammation during pregnancy is associated with the development of preeclampsia, whether maternal inflammation increases the risk of disease later in life is unclear. Using a rat model we determined whether aberrant inflammation in pregnancy alters the levels of plasma proteins associated with cardiovascular and metabolic disease risk in the postpartum period. Pregnant rats were administered lipopolysaccharide (LPS) or saline on gestational days 13.5–16.5 to induce inflammation. Non-pregnant controls consisted of age-matched female rats subjected to similar administration of LPS or saline. Examination of the proteomic profile of plasma collected 16 weeks after delivery or from non-pregnant controls using liquid chromatography-tandem mass spectrometry revealed 100 differentially expressed proteins. Moreover, we identified 188 proteins in pregnant rats, of which 49 were differentially expressed in saline- vs LPS-treated dams. Of the 49 proteins regulated by LPS, 28 were pregnancy specific. PANTHER classification software, DAVID database and Ingenuity Pathways analysis revealed that the differentially expressed proteins in pregnant saline vs LPS-treated rats are associated with alterations in lipid and glucose metabolism and atherosclerosis, all of which may contribute to cardiovascular and metabolic disease risk. Results from proteomic and pathway analyses were validated by immunoassay of three serum proteins selected a priori and by assessment of serum metabolites. This discovery study demonstrates that aberrant inflammation during pregnancy results in long-lasting postpartum physiological alterations known to be associated with metabolic and cardiovascular disease.

Supplementary Materials

    • Supplemental Table 1 Summary of physiological characteristics in pregnancy and postpartum.
    • Supplemental Table 2
    • Supplemental Table 3
    • Supplemental Table 4
    • Supplemental Table 5
    • Supplemental Table 6
    • Supplemental Table 7 Biochemical examination of blood at postpartum 16 weeks.
    • Supplemental figure 1 Networks analysis in IPA Three network functions were generated from 43 differentially expressed proteins. A. Protein Synthesis, Lipid Metabolism, Molecular Transport (score 54; 21 proteins). B. Inflammatory Response, Organismal Injury and Abnormalities, Renal and Urological Disease (score 21; 10 proteins). C. Cell Death and Survival, Dermatological Disease and Conditions, Organismal Injury and Abnormalities (score 21; 10 proteins). The differentially expressed proteins identified in the dataset are highlighted in red (up-regulated) or in green (down-regulated). The intensity of the node color indicates the expression level or degree of regulation. Proteins represented in white were not identified in our dataset. Scores were calculated from hypergeometric distribution and Fisher’s exact test.

 

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