PMID- 37842294 OWN - NLM STAT- MEDLINE DCOM- 20231023 LR - 20231023 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 14 DP - 2023 TI - A comparison of rat models that best mimic immune-driven preeclampsia in humans. PG - 1219205 LID - 10.3389/fendo.2023.1219205 [doi] LID - 1219205 AB - Preeclampsia (PE), a hypertensive pregnancy disorder, can originate from varied etiology. Placenta malperfusion has long been considered the primary cause of PE. However, we and others have showed that this disorder can also result from heightened inflammation at the maternal-fetal interface. To advance our understanding of this understudied PE subtype, it is important to establish validated rodent models to study the pathophysiology and test therapies. We evaluated three previously described approaches to induce inflammation-mediated PE-like features in pregnant rats: 1) Tumor necrosis factor-alpha (TNF-alpha) infusion via osmotic pump from gestational day (GD) 14-19 at 50ng/day/animal; 2) Polyinosinic:polycytidylic acid (Poly I:C) intraperitoneal (IP) injections from GD 10-18 (alternate days) at 10mg/kg/day/animal; and, 3) Lipopolysaccharide (LPS) IP injections from GD 13-18 at 20ug-70ug/kg/day per animal. Maternal blood pressure was measured by tail-cuff. Upon sacrifice, fetal and placenta weights were recorded. Placenta histomorphology was assessed using H&E sections. Placenta inflammation was determined by quantifying TNF-alpha levels and inflammatory gene expression. Placenta metabolic and mitochondrial health were determined by measuring mitochondrial respiration rates and placenta NAD(+)/NADH content. Of the three rodent models tested, we found that Poly I:C and LPS decreased both fetal weight and survival; and correlated with a reduction in region specific placenta growth. As the least effective model characterized, TNF-alpha treatment resulted in a subtle decrease in fetal/placenta weight and placenta mitochondrial respiration. Only the LPS model was able to induce maternal hypertension and exhibited pronounced placenta metabolic and mitochondrial dysfunction, common features of PE. Thus, the rat LPS model was most effective for recapitulating features observed in cases of human inflammatory PE. Future mechanistic and/or therapeutic intervention studies focuses on this distinct PE patient population may benefit from the employment of this rodent model of PE. CI - Copyright (c) 2023 Jahan, Vasam, Cariaco, Nik-Akhtar, Green, Menzies and Bainbridge. FAU - Jahan, Fahmida AU - Jahan F AD - Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada. FAU - Vasam, Goutham AU - Vasam G AD - Interdisciplinary School of Health Sciences, Faculty of Health Sciences, University of Ottawa, Ottawa, ON, Canada. FAU - Cariaco, Yusmaris AU - Cariaco Y AD - Interdisciplinary School of Health Sciences, Faculty of Health Sciences, University of Ottawa, Ottawa, ON, Canada. FAU - Nik-Akhtar, Abolfazl AU - Nik-Akhtar A AD - Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada. FAU - Green, Alex AU - Green A AD - Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada. FAU - Menzies, Keir J AU - Menzies KJ AD - Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada. AD - Interdisciplinary School of Health Sciences, Faculty of Health Sciences, University of Ottawa, Ottawa, ON, Canada. AD - Ottawa Institute of Systems Biology, University of Ottawa, Ottawa, ON, Canada. FAU - Bainbridge, Shannon A AU - Bainbridge SA AD - Interdisciplinary School of Health Sciences, Faculty of Health Sciences, University of Ottawa, Ottawa, ON, Canada. AD - Ottawa Institute of Systems Biology, University of Ottawa, Ottawa, ON, Canada. AD - Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada. LA - eng GR - PJT-153055/CIHR/Canada GR - FRN-167027/CIHR/Canada PT - Journal Article DEP - 20230928 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - 0 (Tumor Necrosis Factor-alpha) RN - 0 (Lipopolysaccharides) RN - 25249-22-3 (Poly I) SB - IM MH - Pregnancy MH - Female MH - Humans MH - Rats MH - Animals MH - *Pre-Eclampsia/metabolism MH - Tumor Necrosis Factor-alpha MH - Lipopolysaccharides MH - *Hypertension MH - Inflammation/metabolism MH - Poly I PMC - PMC10569118 OTO - NOTNLM OT - Poly I:C OT - TNF-alpha OT - disease subclasses OT - hypertension OT - immune OT - preeclampsia OT - pregnancy OT - proinflammatory COIS- 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. EDAT- 2023/10/16 06:48 MHDA- 2023/10/23 01:18 PMCR- 2023/01/01 CRDT- 2023/10/16 04:51 PHST- 2023/05/09 00:00 [received] PHST- 2023/09/04 00:00 [accepted] PHST- 2023/10/23 01:18 [medline] PHST- 2023/10/16 06:48 [pubmed] PHST- 2023/10/16 04:51 [entrez] PHST- 2023/01/01 00:00 [pmc-release] AID - 10.3389/fendo.2023.1219205 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2023 Sep 28;14:1219205. doi: 10.3389/fendo.2023.1219205. eCollection 2023.