A double-hit pre-eclampsia model results in sex-specific growth restriction patterns
Pre-eclampsia is a multifactorial pregnancy-associated disorder characterized by angiogenic dysbalance and systemic inflammation; however, animal models that combine these two pathophysiological conditions are missing. Here, we introduce a novel double-hit pre-eclampsia mouse model that mimics the c...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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The Company of Biologists
2019-02-01
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| Series: | Disease Models & Mechanisms |
| Subjects: | |
| Online Access: | http://dmm.biologists.org/content/12/2/dmm035980 |
| _version_ | 1818449028567793664 |
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| author | Violeta Stojanovska Dorieke J. Dijkstra Rebekka Vogtmann Alexandra Gellhaus Sicco A. Scherjon Torsten Plösch |
| author_facet | Violeta Stojanovska Dorieke J. Dijkstra Rebekka Vogtmann Alexandra Gellhaus Sicco A. Scherjon Torsten Plösch |
| author_sort | Violeta Stojanovska |
| collection | DOAJ |
| description | Pre-eclampsia is a multifactorial pregnancy-associated disorder characterized by angiogenic dysbalance and systemic inflammation; however, animal models that combine these two pathophysiological conditions are missing. Here, we introduce a novel double-hit pre-eclampsia mouse model that mimics the complex multifactorial conditions present during pre-eclampsia and allows for the investigation of early consequences for the fetus. Adenoviral overexpression of soluble fms-like tyrosine kinase (sFlt-1) and lipopolysaccharide (LPS) administration at mid-gestation in pregnant mice resulted in hypertension and albuminuria comparable to that of the manifestation in humans. A metabolomics analysis revealed that pre-eclamptic dams have increased plasma concentrations of phosphadytilcholines. The fetuses of both sexes were growth restricted; however, in males a brain-sparing effect was seen as compensation for this growth restriction. According to the plasma metabolomics, male fetuses showed changes in amino acid metabolism, while female fetuses showed pronounced alterations in lipid metabolism. Our results show that combined exposure to sFlt-1 and LPS mimics the clinical symptoms of pre-eclampsia and affects fetal growth in a sex-specific manner, with accompanying metabolome changes. |
| first_indexed | 2024-12-14T20:28:54Z |
| format | Article |
| id | doaj.art-5b6be1dc1c414b63b67e1a18c93e6ec8 |
| institution | Directory Open Access Journal |
| issn | 1754-8403 1754-8411 |
| language | English |
| last_indexed | 2024-12-14T20:28:54Z |
| publishDate | 2019-02-01 |
| publisher | The Company of Biologists |
| record_format | Article |
| series | Disease Models & Mechanisms |
| spelling | doaj.art-5b6be1dc1c414b63b67e1a18c93e6ec82022-12-21T22:48:34ZengThe Company of BiologistsDisease Models & Mechanisms1754-84031754-84112019-02-0112210.1242/dmm.035980035980A double-hit pre-eclampsia model results in sex-specific growth restriction patternsVioleta Stojanovska0Dorieke J. Dijkstra1Rebekka Vogtmann2Alexandra Gellhaus3Sicco A. Scherjon4Torsten Plösch5 Department of Obstetrics and Gynecology, University Medical Center Groningen, University of Groningen, 9700RB Groningen, The Netherlands Department of Obstetrics and Gynecology, University Medical Center Groningen, University of Groningen, 9700RB Groningen, The Netherlands Department of Gynecology and Obstetrics, University Hospital Duisburg-Essen, 45147 Essen, Germany Department of Gynecology and Obstetrics, University Hospital Duisburg-Essen, 45147 Essen, Germany Department of Obstetrics and Gynecology, University Medical Center Groningen, University of Groningen, 9700RB Groningen, The Netherlands Department of Obstetrics and Gynecology, University Medical Center Groningen, University of Groningen, 9700RB Groningen, The Netherlands Pre-eclampsia is a multifactorial pregnancy-associated disorder characterized by angiogenic dysbalance and systemic inflammation; however, animal models that combine these two pathophysiological conditions are missing. Here, we introduce a novel double-hit pre-eclampsia mouse model that mimics the complex multifactorial conditions present during pre-eclampsia and allows for the investigation of early consequences for the fetus. Adenoviral overexpression of soluble fms-like tyrosine kinase (sFlt-1) and lipopolysaccharide (LPS) administration at mid-gestation in pregnant mice resulted in hypertension and albuminuria comparable to that of the manifestation in humans. A metabolomics analysis revealed that pre-eclamptic dams have increased plasma concentrations of phosphadytilcholines. The fetuses of both sexes were growth restricted; however, in males a brain-sparing effect was seen as compensation for this growth restriction. According to the plasma metabolomics, male fetuses showed changes in amino acid metabolism, while female fetuses showed pronounced alterations in lipid metabolism. Our results show that combined exposure to sFlt-1 and LPS mimics the clinical symptoms of pre-eclampsia and affects fetal growth in a sex-specific manner, with accompanying metabolome changes.http://dmm.biologists.org/content/12/2/dmm035980Developmental programmingMetabolomicsPre-eclampsia |
| spellingShingle | Violeta Stojanovska Dorieke J. Dijkstra Rebekka Vogtmann Alexandra Gellhaus Sicco A. Scherjon Torsten Plösch A double-hit pre-eclampsia model results in sex-specific growth restriction patterns Disease Models & Mechanisms Developmental programming Metabolomics Pre-eclampsia |
| title | A double-hit pre-eclampsia model results in sex-specific growth restriction patterns |
| title_full | A double-hit pre-eclampsia model results in sex-specific growth restriction patterns |
| title_fullStr | A double-hit pre-eclampsia model results in sex-specific growth restriction patterns |
| title_full_unstemmed | A double-hit pre-eclampsia model results in sex-specific growth restriction patterns |
| title_short | A double-hit pre-eclampsia model results in sex-specific growth restriction patterns |
| title_sort | double hit pre eclampsia model results in sex specific growth restriction patterns |
| topic | Developmental programming Metabolomics Pre-eclampsia |
| url | http://dmm.biologists.org/content/12/2/dmm035980 |
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