Innate immune system stimulation during pregnancy induces upregulation of thromboxane synthesis in rat maternal heart
dc.creator | Tucker, Selina | |
dc.creator | Cushen, Spencer | |
dc.creator | Bradshaw, Jessica L. | |
dc.creator | Gardner, Jennifer | |
dc.creator | Ricci, Contessa | |
dc.creator | Dick, Gregory | |
dc.creator | Tune, Johnathan | |
dc.creator | Goulopoulou, Styliani | |
dc.creator.orcid | 0000-0002-7959-8716 (Tucker, Selina) | |
dc.creator.orcid | 0000-0003-3784-9190 (Gardner, Jennifer) | |
dc.date.accessioned | 2022-05-10T18:05:26Z | |
dc.date.available | 2022-05-10T18:05:26Z | |
dc.date.issued | 2022 | |
dc.description.abstract | Purpose: Infections during pregnancy are associated with adverse clinical outcomes. We previously showed that exposure to immunostimulatory ODN2395 (synthetic Toll-like receptor 9 agonist) during pregnancy induces maternal vascular inflammation and enhances vascular tone in pregnant rats. These outcomes were mediated in part by activation of the cyclooxygenase/thromboxane A2 (COX/TxA2) pathway. The objective of this study was to investigate the impact of ODN2395-induced immune system stimulation on maternal hearts during pregnancy. We hypothesize that exposure to TLR9-mediated immune system activation during pregnancy upregulates the COX/TxA2 signaling pathway in maternal cardiac tissues in rats. Methods: Rats were treated with a synthetic CpG DNA (ODN2395, 1 mg/kg, intraperitoneal injection) or vehicle (saline) in late pregnancy. Fetoplacental biometrics were recorded after euthanasia on gestational day 20 and maternal hearts were collected to assess COX-1 and COX-2 expression and 6-keto PGF1α (PGI2 metabolic byproduct) and TxB2 (TxA2 metabolic byproduct) production. Results: Left ventricular tissues from dams treated with ODN2395 released higher concentrations of TxB2 compared to tissues from vehicle-treated dams (ODN2395: 0.56 ± 0.06 ng/mg protein vs. Vehicle: 0.31 ± 0.04 ng/mg protein, n5, p=0.0041) but there were no differences in cardiac 6-keto PGF1α release between groups (p=0.16). COX-2 expression was lower in left ventricles from ODN2395-treated rats compared to vehicle-treated rats (p=0.009). There were no differences in cardiac COX-1 expression between groups (p=0.27). Exposure to ODN2395 during pregnancy increased fetal-placental weight ratio (ODN2395: 5.3 ± 0.22 vs. Vehicle: 4.7 ± 0.15, p = 0.04). COX-2 expression was greater in placental tissues from ODN2395-treated rats (p=0.004) but there were no differences in placental 6-keto PGF1α (p=0.51) and TxB2 release (p=0.32). Conclusion: TLR9 activation during pregnancy induces upregulation of TxB2 synthesis in maternal cardiac tissues coupled with a reduction in COX-2 expression. Maternal heart may have enhanced sensitivity to bacterial infections during pregnancy. | |
dc.description.sponsorship | NIHR018L146562, 18PRE33960162, T32AG020494, NIH R25GM125587 | |
dc.identifier.uri | https://hdl.handle.net/20.500.12503/30959 | |
dc.language.iso | en | |
dc.title | Innate immune system stimulation during pregnancy induces upregulation of thromboxane synthesis in rat maternal heart | |
dc.type | poster | |
dc.type.material | text |