Distinct phenotypes in the preeclamptic-like mouse model induced by adenovirus carrying sFlt1 and recombinant sFlt1 protein

Abstract Background Preeclampsia (PE) is a pregnancy-specific, multisystemic disorder that affects 2–8% pregnancies worldwide and is a leading cause of maternal and perinatal mortality. At present, there is no cure for PE apart from delivery the placenta. Therefore, it is important and urgent to pos...

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Main Authors: Yingying Wei, Haojun Tian, Xuancheng Wei, Ai Zhang, Mengtian Wei, Ruixue Wang, Lu Zhang, Ping Qiao, Kai Wang
Format: Article
Language:English
Published: BMC 2024-12-01
Series:European Journal of Medical Research
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Online Access:https://doi.org/10.1186/s40001-024-02223-6
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author Yingying Wei
Haojun Tian
Xuancheng Wei
Ai Zhang
Mengtian Wei
Ruixue Wang
Lu Zhang
Ping Qiao
Kai Wang
author_facet Yingying Wei
Haojun Tian
Xuancheng Wei
Ai Zhang
Mengtian Wei
Ruixue Wang
Lu Zhang
Ping Qiao
Kai Wang
author_sort Yingying Wei
collection DOAJ
description Abstract Background Preeclampsia (PE) is a pregnancy-specific, multisystemic disorder that affects 2–8% pregnancies worldwide and is a leading cause of maternal and perinatal mortality. At present, there is no cure for PE apart from delivery the placenta. Therefore, it is important and urgent to possess a suitable animal model to study the pathology and treatment of PE. When exogenous soluble fms-like tyrosine kinase-1 (sFlt-1) is administered, pregnant animals develop a PE-like phenotype. However, there is no report on the comparison between different methods of constructing PE mouse models using sFlt-1. Methods In this study, the adenovirus carrying sFlt-1(ADV-Flt-1) and recombinant murine sFlt-1 protein (RM Flt-1) are two different methods were used to induce and compare PE-like mouse models. Pregnancy outcomes were examined on E14.5 and E17.5. Results Our data showed that on E14.5, the adenovirus carrying sFlt-1 induced PE-like phenotype, whereas recombinant murine sFlt-1 protein not. On E17.5, both the two methods induced PE-like phenotype including hypertension, proteinuria, fetal growth restriction, placental and glomerular endotheliosis. Importantly, in the adenoviral-mediated sFlt-1 group, the circulating concentration of sFlt-1 were higher than in the recombinant sFlt-1 group, leading to earlier and more severe symptoms of PE. The ADV-Flt-1 group is easy to operate, quickly effective and efficient. The RM Flt-1 group is safer and more stable, with good repeatability, but slower to take effect. Conclusions We proposed that the adenoviral-mediated sFlt-1 model can better simulate early-onset and severe PE.
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series European Journal of Medical Research
spelling doaj-art-263b050c12444a5ebaaefd2fd5e4c27f2025-01-05T12:12:16ZengBMCEuropean Journal of Medical Research2047-783X2024-12-0129111210.1186/s40001-024-02223-6Distinct phenotypes in the preeclamptic-like mouse model induced by adenovirus carrying sFlt1 and recombinant sFlt1 proteinYingying Wei0Haojun Tian1Xuancheng Wei2Ai Zhang3Mengtian Wei4Ruixue Wang5Lu Zhang6Ping Qiao7Kai Wang8Clinical and Translational Research Center, Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji UniversityClinical and Translational Research Center, Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji UniversityClinical and Translational Research Center, Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji UniversityFetal Medicine Center, Qingdao Women and Children’s Hospital, Qingdao UniversityClinical and Translational Research Center, Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji UniversityClinical and Translational Research Center, Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji UniversityClinical and Translational Research Center, Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji UniversityDepartment of Obstetrics, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji UniversityClinical and Translational Research Center, Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji UniversityAbstract Background Preeclampsia (PE) is a pregnancy-specific, multisystemic disorder that affects 2–8% pregnancies worldwide and is a leading cause of maternal and perinatal mortality. At present, there is no cure for PE apart from delivery the placenta. Therefore, it is important and urgent to possess a suitable animal model to study the pathology and treatment of PE. When exogenous soluble fms-like tyrosine kinase-1 (sFlt-1) is administered, pregnant animals develop a PE-like phenotype. However, there is no report on the comparison between different methods of constructing PE mouse models using sFlt-1. Methods In this study, the adenovirus carrying sFlt-1(ADV-Flt-1) and recombinant murine sFlt-1 protein (RM Flt-1) are two different methods were used to induce and compare PE-like mouse models. Pregnancy outcomes were examined on E14.5 and E17.5. Results Our data showed that on E14.5, the adenovirus carrying sFlt-1 induced PE-like phenotype, whereas recombinant murine sFlt-1 protein not. On E17.5, both the two methods induced PE-like phenotype including hypertension, proteinuria, fetal growth restriction, placental and glomerular endotheliosis. Importantly, in the adenoviral-mediated sFlt-1 group, the circulating concentration of sFlt-1 were higher than in the recombinant sFlt-1 group, leading to earlier and more severe symptoms of PE. The ADV-Flt-1 group is easy to operate, quickly effective and efficient. The RM Flt-1 group is safer and more stable, with good repeatability, but slower to take effect. Conclusions We proposed that the adenoviral-mediated sFlt-1 model can better simulate early-onset and severe PE.https://doi.org/10.1186/s40001-024-02223-6PreeclampsiaAdenovirusSoluble fms-like tyrosine kinase-1MiceModel
spellingShingle Yingying Wei
Haojun Tian
Xuancheng Wei
Ai Zhang
Mengtian Wei
Ruixue Wang
Lu Zhang
Ping Qiao
Kai Wang
Distinct phenotypes in the preeclamptic-like mouse model induced by adenovirus carrying sFlt1 and recombinant sFlt1 protein
European Journal of Medical Research
Preeclampsia
Adenovirus
Soluble fms-like tyrosine kinase-1
Mice
Model
title Distinct phenotypes in the preeclamptic-like mouse model induced by adenovirus carrying sFlt1 and recombinant sFlt1 protein
title_full Distinct phenotypes in the preeclamptic-like mouse model induced by adenovirus carrying sFlt1 and recombinant sFlt1 protein
title_fullStr Distinct phenotypes in the preeclamptic-like mouse model induced by adenovirus carrying sFlt1 and recombinant sFlt1 protein
title_full_unstemmed Distinct phenotypes in the preeclamptic-like mouse model induced by adenovirus carrying sFlt1 and recombinant sFlt1 protein
title_short Distinct phenotypes in the preeclamptic-like mouse model induced by adenovirus carrying sFlt1 and recombinant sFlt1 protein
title_sort distinct phenotypes in the preeclamptic like mouse model induced by adenovirus carrying sflt1 and recombinant sflt1 protein
topic Preeclampsia
Adenovirus
Soluble fms-like tyrosine kinase-1
Mice
Model
url https://doi.org/10.1186/s40001-024-02223-6
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