Sustained Endocrine Gland-Derived Vascular Endothelial Growth Factor Levels Beyond the First Trimester of Pregnancy Display Phenotypic and Functional Changes Associated With the Pathogenesis of Pregnancy-Induced Hypertension.
Identifieur interne : 001B93 ( PubMed/Corpus ); précédent : 001B92; suivant : 001B94Sustained Endocrine Gland-Derived Vascular Endothelial Growth Factor Levels Beyond the First Trimester of Pregnancy Display Phenotypic and Functional Changes Associated With the Pathogenesis of Pregnancy-Induced Hypertension.
Auteurs : Frédéric Sergent ; Pascale Hoffmann ; Sophie Brouillet ; Vanessa Garnier ; Aude Salomon ; Padma Murthi ; Mohamed Benharouga ; Jean-Jacques Feige ; Nadia AlfaidySource :
- Hypertension (Dallas, Tex. : 1979) [ 1524-4563 ] ; 2016.
English descriptors
- KwdEn :
- Animals, Biopsy, Needle, Blotting, Western, Disease Models, Animal, Female, Hypertension, Pregnancy-Induced (genetics), Hypertension, Pregnancy-Induced (physiopathology), Immunohistochemistry, Mice, Mice, Inbred Strains, Phenotype, Placenta (drug effects), Placenta (pathology), Pregnancy, Pregnancy Trimester, First, Pregnancy, Animal, Random Allocation, Real-Time Polymerase Chain Reaction (methods), Receptors, G-Protein-Coupled (genetics), Sensitivity and Specificity, Vascular Endothelial Growth Factor, Endocrine-Gland-Derived (blood), Vascular Endothelial Growth Factor, Endocrine-Gland-Derived (pharmacology).
- MESH :
- chemical , blood : Vascular Endothelial Growth Factor, Endocrine-Gland-Derived.
- chemical , genetics : Receptors, G-Protein-Coupled.
- drug effects : Placenta.
- genetics : Hypertension, Pregnancy-Induced.
- methods : Real-Time Polymerase Chain Reaction.
- pathology : Placenta.
- chemical , pharmacology : Vascular Endothelial Growth Factor, Endocrine-Gland-Derived.
- physiopathology : Hypertension, Pregnancy-Induced.
- Animals, Biopsy, Needle, Blotting, Western, Disease Models, Animal, Female, Immunohistochemistry, Mice, Mice, Inbred Strains, Phenotype, Pregnancy, Pregnancy Trimester, First, Pregnancy, Animal, Random Allocation, Sensitivity and Specificity.
Abstract
Pregnancy-induced hypertension diseases are classified as gestational hypertension, preeclampsia, or eclampsia. The mechanisms of their development and prediction are still to be discovered. Endocrine gland-derived vascular endothelial growth factor (EG-VEGF) is an angiogenic factor secreted by the placenta during the first trimester of human pregnancy that was shown to control trophoblast invasion, to be upregulated by hypoxia, and to be abnormally elevated in pathological pregnancies complicated with preeclampsia and intrauterine growth restriction. These findings suggested that sustaining EG-VEGF levels beyond the first trimester of pregnancy may contribute to pregnancy-induced hypertension. To test this hypothesis, osmotic minipumps delivering EG-VEGF were implanted subcutaneously into gravid OF1 (Oncins France 1) mice on day 11.5 post coitus, which is equivalent to the end of the first trimester of human pregnancy. Mice were euthanized at 15.5 and 18.5 days post coitus to assess (1) litter size, placental, and fetal weights; (2) placental histology and function; (3) maternal blood pressure; (4) renal histology and function; and (5) circulating soluble fms-like tyrosine kinase 1 and soluble endoglin. Increased EG-VEGF levels caused significant defects in placental organization and function. Both increased hypoxia and decreased trophoblast invasion were observed. Treated mice had elevated circulating soluble fms-like tyrosine kinase 1 and soluble endoglin and developed gestational hypertension with dysregulated maternal kidney function. EG-VEGF effect on the kidney function was secondary to its effects on the placenta as similarly treated male mice had normal kidney functions. Altogether, these data provide a strong evidence to confirm that sustained EG-VEGF beyond the first trimester of pregnancy contributes to the development of pregnancy-induced hypertension.
DOI: 10.1161/HYPERTENSIONAHA.116.07442
PubMed: 27141059
Links to Exploration step
pubmed:27141059Le document en format XML
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<author><name sortKey="Sergent, Frederic" sort="Sergent, Frederic" uniqKey="Sergent F" first="Frédéric" last="Sergent">Frédéric Sergent</name>
<affiliation><nlm:affiliation>From the Institut National de la Santé et de la Recherche Médicale, Grenoble, France (F.S., P.H., S.B., V.G., A.S., J.-J.F., N.A.); University Grenoble-Alpes, Grenoble, France (F.S., P.H., S.B., V.G., A.S., M.B., J.-J.F., N.A.); Commissariat à l'Energie Atomique (CEA), BIG (Biosciences Biotechnology Institute of Grenoble)-Biology of Cancer and Infection, Grenoble, France (F.S., P.H., S.B., V.G., A.S., M.B., J.-J.F., N.A.); Department of Obstetrics and Gynaecology, University Hospital of Grenoble, La Tronche, France (P.H.); Laboratoire d'Aide à la Procréation-CECOS, University Hospital of Grenoble, La Tronche, France (S.B.); Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5249, Laboratoire de Chimie et Biologie des Métaux, Grenoble, France (M.B.); and Department of Medicine, School of Clinical Sciences, Monash university and the Ritchie Centre, Hudson Institute of Medical Research, Clayton, Victoria, Australia (P.M.).</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Hoffmann, Pascale" sort="Hoffmann, Pascale" uniqKey="Hoffmann P" first="Pascale" last="Hoffmann">Pascale Hoffmann</name>
<affiliation><nlm:affiliation>From the Institut National de la Santé et de la Recherche Médicale, Grenoble, France (F.S., P.H., S.B., V.G., A.S., J.-J.F., N.A.); University Grenoble-Alpes, Grenoble, France (F.S., P.H., S.B., V.G., A.S., M.B., J.-J.F., N.A.); Commissariat à l'Energie Atomique (CEA), BIG (Biosciences Biotechnology Institute of Grenoble)-Biology of Cancer and Infection, Grenoble, France (F.S., P.H., S.B., V.G., A.S., M.B., J.-J.F., N.A.); Department of Obstetrics and Gynaecology, University Hospital of Grenoble, La Tronche, France (P.H.); Laboratoire d'Aide à la Procréation-CECOS, University Hospital of Grenoble, La Tronche, France (S.B.); Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5249, Laboratoire de Chimie et Biologie des Métaux, Grenoble, France (M.B.); and Department of Medicine, School of Clinical Sciences, Monash university and the Ritchie Centre, Hudson Institute of Medical Research, Clayton, Victoria, Australia (P.M.).</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Brouillet, Sophie" sort="Brouillet, Sophie" uniqKey="Brouillet S" first="Sophie" last="Brouillet">Sophie Brouillet</name>
<affiliation><nlm:affiliation>From the Institut National de la Santé et de la Recherche Médicale, Grenoble, France (F.S., P.H., S.B., V.G., A.S., J.-J.F., N.A.); University Grenoble-Alpes, Grenoble, France (F.S., P.H., S.B., V.G., A.S., M.B., J.-J.F., N.A.); Commissariat à l'Energie Atomique (CEA), BIG (Biosciences Biotechnology Institute of Grenoble)-Biology of Cancer and Infection, Grenoble, France (F.S., P.H., S.B., V.G., A.S., M.B., J.-J.F., N.A.); Department of Obstetrics and Gynaecology, University Hospital of Grenoble, La Tronche, France (P.H.); Laboratoire d'Aide à la Procréation-CECOS, University Hospital of Grenoble, La Tronche, France (S.B.); Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5249, Laboratoire de Chimie et Biologie des Métaux, Grenoble, France (M.B.); and Department of Medicine, School of Clinical Sciences, Monash university and the Ritchie Centre, Hudson Institute of Medical Research, Clayton, Victoria, Australia (P.M.).</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Garnier, Vanessa" sort="Garnier, Vanessa" uniqKey="Garnier V" first="Vanessa" last="Garnier">Vanessa Garnier</name>
<affiliation><nlm:affiliation>From the Institut National de la Santé et de la Recherche Médicale, Grenoble, France (F.S., P.H., S.B., V.G., A.S., J.-J.F., N.A.); University Grenoble-Alpes, Grenoble, France (F.S., P.H., S.B., V.G., A.S., M.B., J.-J.F., N.A.); Commissariat à l'Energie Atomique (CEA), BIG (Biosciences Biotechnology Institute of Grenoble)-Biology of Cancer and Infection, Grenoble, France (F.S., P.H., S.B., V.G., A.S., M.B., J.-J.F., N.A.); Department of Obstetrics and Gynaecology, University Hospital of Grenoble, La Tronche, France (P.H.); Laboratoire d'Aide à la Procréation-CECOS, University Hospital of Grenoble, La Tronche, France (S.B.); Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5249, Laboratoire de Chimie et Biologie des Métaux, Grenoble, France (M.B.); and Department of Medicine, School of Clinical Sciences, Monash university and the Ritchie Centre, Hudson Institute of Medical Research, Clayton, Victoria, Australia (P.M.).</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Salomon, Aude" sort="Salomon, Aude" uniqKey="Salomon A" first="Aude" last="Salomon">Aude Salomon</name>
<affiliation><nlm:affiliation>From the Institut National de la Santé et de la Recherche Médicale, Grenoble, France (F.S., P.H., S.B., V.G., A.S., J.-J.F., N.A.); University Grenoble-Alpes, Grenoble, France (F.S., P.H., S.B., V.G., A.S., M.B., J.-J.F., N.A.); Commissariat à l'Energie Atomique (CEA), BIG (Biosciences Biotechnology Institute of Grenoble)-Biology of Cancer and Infection, Grenoble, France (F.S., P.H., S.B., V.G., A.S., M.B., J.-J.F., N.A.); Department of Obstetrics and Gynaecology, University Hospital of Grenoble, La Tronche, France (P.H.); Laboratoire d'Aide à la Procréation-CECOS, University Hospital of Grenoble, La Tronche, France (S.B.); Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5249, Laboratoire de Chimie et Biologie des Métaux, Grenoble, France (M.B.); and Department of Medicine, School of Clinical Sciences, Monash university and the Ritchie Centre, Hudson Institute of Medical Research, Clayton, Victoria, Australia (P.M.).</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Murthi, Padma" sort="Murthi, Padma" uniqKey="Murthi P" first="Padma" last="Murthi">Padma Murthi</name>
<affiliation><nlm:affiliation>From the Institut National de la Santé et de la Recherche Médicale, Grenoble, France (F.S., P.H., S.B., V.G., A.S., J.-J.F., N.A.); University Grenoble-Alpes, Grenoble, France (F.S., P.H., S.B., V.G., A.S., M.B., J.-J.F., N.A.); Commissariat à l'Energie Atomique (CEA), BIG (Biosciences Biotechnology Institute of Grenoble)-Biology of Cancer and Infection, Grenoble, France (F.S., P.H., S.B., V.G., A.S., M.B., J.-J.F., N.A.); Department of Obstetrics and Gynaecology, University Hospital of Grenoble, La Tronche, France (P.H.); Laboratoire d'Aide à la Procréation-CECOS, University Hospital of Grenoble, La Tronche, France (S.B.); Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5249, Laboratoire de Chimie et Biologie des Métaux, Grenoble, France (M.B.); and Department of Medicine, School of Clinical Sciences, Monash university and the Ritchie Centre, Hudson Institute of Medical Research, Clayton, Victoria, Australia (P.M.).</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Benharouga, Mohamed" sort="Benharouga, Mohamed" uniqKey="Benharouga M" first="Mohamed" last="Benharouga">Mohamed Benharouga</name>
<affiliation><nlm:affiliation>From the Institut National de la Santé et de la Recherche Médicale, Grenoble, France (F.S., P.H., S.B., V.G., A.S., J.-J.F., N.A.); University Grenoble-Alpes, Grenoble, France (F.S., P.H., S.B., V.G., A.S., M.B., J.-J.F., N.A.); Commissariat à l'Energie Atomique (CEA), BIG (Biosciences Biotechnology Institute of Grenoble)-Biology of Cancer and Infection, Grenoble, France (F.S., P.H., S.B., V.G., A.S., M.B., J.-J.F., N.A.); Department of Obstetrics and Gynaecology, University Hospital of Grenoble, La Tronche, France (P.H.); Laboratoire d'Aide à la Procréation-CECOS, University Hospital of Grenoble, La Tronche, France (S.B.); Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5249, Laboratoire de Chimie et Biologie des Métaux, Grenoble, France (M.B.); and Department of Medicine, School of Clinical Sciences, Monash university and the Ritchie Centre, Hudson Institute of Medical Research, Clayton, Victoria, Australia (P.M.).</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Feige, Jean Jacques" sort="Feige, Jean Jacques" uniqKey="Feige J" first="Jean-Jacques" last="Feige">Jean-Jacques Feige</name>
<affiliation><nlm:affiliation>From the Institut National de la Santé et de la Recherche Médicale, Grenoble, France (F.S., P.H., S.B., V.G., A.S., J.-J.F., N.A.); University Grenoble-Alpes, Grenoble, France (F.S., P.H., S.B., V.G., A.S., M.B., J.-J.F., N.A.); Commissariat à l'Energie Atomique (CEA), BIG (Biosciences Biotechnology Institute of Grenoble)-Biology of Cancer and Infection, Grenoble, France (F.S., P.H., S.B., V.G., A.S., M.B., J.-J.F., N.A.); Department of Obstetrics and Gynaecology, University Hospital of Grenoble, La Tronche, France (P.H.); Laboratoire d'Aide à la Procréation-CECOS, University Hospital of Grenoble, La Tronche, France (S.B.); Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5249, Laboratoire de Chimie et Biologie des Métaux, Grenoble, France (M.B.); and Department of Medicine, School of Clinical Sciences, Monash university and the Ritchie Centre, Hudson Institute of Medical Research, Clayton, Victoria, Australia (P.M.).</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Alfaidy, Nadia" sort="Alfaidy, Nadia" uniqKey="Alfaidy N" first="Nadia" last="Alfaidy">Nadia Alfaidy</name>
<affiliation><nlm:affiliation>From the Institut National de la Santé et de la Recherche Médicale, Grenoble, France (F.S., P.H., S.B., V.G., A.S., J.-J.F., N.A.); University Grenoble-Alpes, Grenoble, France (F.S., P.H., S.B., V.G., A.S., M.B., J.-J.F., N.A.); Commissariat à l'Energie Atomique (CEA), BIG (Biosciences Biotechnology Institute of Grenoble)-Biology of Cancer and Infection, Grenoble, France (F.S., P.H., S.B., V.G., A.S., M.B., J.-J.F., N.A.); Department of Obstetrics and Gynaecology, University Hospital of Grenoble, La Tronche, France (P.H.); Laboratoire d'Aide à la Procréation-CECOS, University Hospital of Grenoble, La Tronche, France (S.B.); Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5249, Laboratoire de Chimie et Biologie des Métaux, Grenoble, France (M.B.); and Department of Medicine, School of Clinical Sciences, Monash university and the Ritchie Centre, Hudson Institute of Medical Research, Clayton, Victoria, Australia (P.M.).</nlm:affiliation>
</affiliation>
</author>
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<sourceDesc><biblStruct><analytic><title xml:lang="en">Sustained Endocrine Gland-Derived Vascular Endothelial Growth Factor Levels Beyond the First Trimester of Pregnancy Display Phenotypic and Functional Changes Associated With the Pathogenesis of Pregnancy-Induced Hypertension.</title>
<author><name sortKey="Sergent, Frederic" sort="Sergent, Frederic" uniqKey="Sergent F" first="Frédéric" last="Sergent">Frédéric Sergent</name>
<affiliation><nlm:affiliation>From the Institut National de la Santé et de la Recherche Médicale, Grenoble, France (F.S., P.H., S.B., V.G., A.S., J.-J.F., N.A.); University Grenoble-Alpes, Grenoble, France (F.S., P.H., S.B., V.G., A.S., M.B., J.-J.F., N.A.); Commissariat à l'Energie Atomique (CEA), BIG (Biosciences Biotechnology Institute of Grenoble)-Biology of Cancer and Infection, Grenoble, France (F.S., P.H., S.B., V.G., A.S., M.B., J.-J.F., N.A.); Department of Obstetrics and Gynaecology, University Hospital of Grenoble, La Tronche, France (P.H.); Laboratoire d'Aide à la Procréation-CECOS, University Hospital of Grenoble, La Tronche, France (S.B.); Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5249, Laboratoire de Chimie et Biologie des Métaux, Grenoble, France (M.B.); and Department of Medicine, School of Clinical Sciences, Monash university and the Ritchie Centre, Hudson Institute of Medical Research, Clayton, Victoria, Australia (P.M.).</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Hoffmann, Pascale" sort="Hoffmann, Pascale" uniqKey="Hoffmann P" first="Pascale" last="Hoffmann">Pascale Hoffmann</name>
<affiliation><nlm:affiliation>From the Institut National de la Santé et de la Recherche Médicale, Grenoble, France (F.S., P.H., S.B., V.G., A.S., J.-J.F., N.A.); University Grenoble-Alpes, Grenoble, France (F.S., P.H., S.B., V.G., A.S., M.B., J.-J.F., N.A.); Commissariat à l'Energie Atomique (CEA), BIG (Biosciences Biotechnology Institute of Grenoble)-Biology of Cancer and Infection, Grenoble, France (F.S., P.H., S.B., V.G., A.S., M.B., J.-J.F., N.A.); Department of Obstetrics and Gynaecology, University Hospital of Grenoble, La Tronche, France (P.H.); Laboratoire d'Aide à la Procréation-CECOS, University Hospital of Grenoble, La Tronche, France (S.B.); Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5249, Laboratoire de Chimie et Biologie des Métaux, Grenoble, France (M.B.); and Department of Medicine, School of Clinical Sciences, Monash university and the Ritchie Centre, Hudson Institute of Medical Research, Clayton, Victoria, Australia (P.M.).</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Brouillet, Sophie" sort="Brouillet, Sophie" uniqKey="Brouillet S" first="Sophie" last="Brouillet">Sophie Brouillet</name>
<affiliation><nlm:affiliation>From the Institut National de la Santé et de la Recherche Médicale, Grenoble, France (F.S., P.H., S.B., V.G., A.S., J.-J.F., N.A.); University Grenoble-Alpes, Grenoble, France (F.S., P.H., S.B., V.G., A.S., M.B., J.-J.F., N.A.); Commissariat à l'Energie Atomique (CEA), BIG (Biosciences Biotechnology Institute of Grenoble)-Biology of Cancer and Infection, Grenoble, France (F.S., P.H., S.B., V.G., A.S., M.B., J.-J.F., N.A.); Department of Obstetrics and Gynaecology, University Hospital of Grenoble, La Tronche, France (P.H.); Laboratoire d'Aide à la Procréation-CECOS, University Hospital of Grenoble, La Tronche, France (S.B.); Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5249, Laboratoire de Chimie et Biologie des Métaux, Grenoble, France (M.B.); and Department of Medicine, School of Clinical Sciences, Monash university and the Ritchie Centre, Hudson Institute of Medical Research, Clayton, Victoria, Australia (P.M.).</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Garnier, Vanessa" sort="Garnier, Vanessa" uniqKey="Garnier V" first="Vanessa" last="Garnier">Vanessa Garnier</name>
<affiliation><nlm:affiliation>From the Institut National de la Santé et de la Recherche Médicale, Grenoble, France (F.S., P.H., S.B., V.G., A.S., J.-J.F., N.A.); University Grenoble-Alpes, Grenoble, France (F.S., P.H., S.B., V.G., A.S., M.B., J.-J.F., N.A.); Commissariat à l'Energie Atomique (CEA), BIG (Biosciences Biotechnology Institute of Grenoble)-Biology of Cancer and Infection, Grenoble, France (F.S., P.H., S.B., V.G., A.S., M.B., J.-J.F., N.A.); Department of Obstetrics and Gynaecology, University Hospital of Grenoble, La Tronche, France (P.H.); Laboratoire d'Aide à la Procréation-CECOS, University Hospital of Grenoble, La Tronche, France (S.B.); Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5249, Laboratoire de Chimie et Biologie des Métaux, Grenoble, France (M.B.); and Department of Medicine, School of Clinical Sciences, Monash university and the Ritchie Centre, Hudson Institute of Medical Research, Clayton, Victoria, Australia (P.M.).</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Salomon, Aude" sort="Salomon, Aude" uniqKey="Salomon A" first="Aude" last="Salomon">Aude Salomon</name>
<affiliation><nlm:affiliation>From the Institut National de la Santé et de la Recherche Médicale, Grenoble, France (F.S., P.H., S.B., V.G., A.S., J.-J.F., N.A.); University Grenoble-Alpes, Grenoble, France (F.S., P.H., S.B., V.G., A.S., M.B., J.-J.F., N.A.); Commissariat à l'Energie Atomique (CEA), BIG (Biosciences Biotechnology Institute of Grenoble)-Biology of Cancer and Infection, Grenoble, France (F.S., P.H., S.B., V.G., A.S., M.B., J.-J.F., N.A.); Department of Obstetrics and Gynaecology, University Hospital of Grenoble, La Tronche, France (P.H.); Laboratoire d'Aide à la Procréation-CECOS, University Hospital of Grenoble, La Tronche, France (S.B.); Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5249, Laboratoire de Chimie et Biologie des Métaux, Grenoble, France (M.B.); and Department of Medicine, School of Clinical Sciences, Monash university and the Ritchie Centre, Hudson Institute of Medical Research, Clayton, Victoria, Australia (P.M.).</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Murthi, Padma" sort="Murthi, Padma" uniqKey="Murthi P" first="Padma" last="Murthi">Padma Murthi</name>
<affiliation><nlm:affiliation>From the Institut National de la Santé et de la Recherche Médicale, Grenoble, France (F.S., P.H., S.B., V.G., A.S., J.-J.F., N.A.); University Grenoble-Alpes, Grenoble, France (F.S., P.H., S.B., V.G., A.S., M.B., J.-J.F., N.A.); Commissariat à l'Energie Atomique (CEA), BIG (Biosciences Biotechnology Institute of Grenoble)-Biology of Cancer and Infection, Grenoble, France (F.S., P.H., S.B., V.G., A.S., M.B., J.-J.F., N.A.); Department of Obstetrics and Gynaecology, University Hospital of Grenoble, La Tronche, France (P.H.); Laboratoire d'Aide à la Procréation-CECOS, University Hospital of Grenoble, La Tronche, France (S.B.); Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5249, Laboratoire de Chimie et Biologie des Métaux, Grenoble, France (M.B.); and Department of Medicine, School of Clinical Sciences, Monash university and the Ritchie Centre, Hudson Institute of Medical Research, Clayton, Victoria, Australia (P.M.).</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Benharouga, Mohamed" sort="Benharouga, Mohamed" uniqKey="Benharouga M" first="Mohamed" last="Benharouga">Mohamed Benharouga</name>
<affiliation><nlm:affiliation>From the Institut National de la Santé et de la Recherche Médicale, Grenoble, France (F.S., P.H., S.B., V.G., A.S., J.-J.F., N.A.); University Grenoble-Alpes, Grenoble, France (F.S., P.H., S.B., V.G., A.S., M.B., J.-J.F., N.A.); Commissariat à l'Energie Atomique (CEA), BIG (Biosciences Biotechnology Institute of Grenoble)-Biology of Cancer and Infection, Grenoble, France (F.S., P.H., S.B., V.G., A.S., M.B., J.-J.F., N.A.); Department of Obstetrics and Gynaecology, University Hospital of Grenoble, La Tronche, France (P.H.); Laboratoire d'Aide à la Procréation-CECOS, University Hospital of Grenoble, La Tronche, France (S.B.); Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5249, Laboratoire de Chimie et Biologie des Métaux, Grenoble, France (M.B.); and Department of Medicine, School of Clinical Sciences, Monash university and the Ritchie Centre, Hudson Institute of Medical Research, Clayton, Victoria, Australia (P.M.).</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Feige, Jean Jacques" sort="Feige, Jean Jacques" uniqKey="Feige J" first="Jean-Jacques" last="Feige">Jean-Jacques Feige</name>
<affiliation><nlm:affiliation>From the Institut National de la Santé et de la Recherche Médicale, Grenoble, France (F.S., P.H., S.B., V.G., A.S., J.-J.F., N.A.); University Grenoble-Alpes, Grenoble, France (F.S., P.H., S.B., V.G., A.S., M.B., J.-J.F., N.A.); Commissariat à l'Energie Atomique (CEA), BIG (Biosciences Biotechnology Institute of Grenoble)-Biology of Cancer and Infection, Grenoble, France (F.S., P.H., S.B., V.G., A.S., M.B., J.-J.F., N.A.); Department of Obstetrics and Gynaecology, University Hospital of Grenoble, La Tronche, France (P.H.); Laboratoire d'Aide à la Procréation-CECOS, University Hospital of Grenoble, La Tronche, France (S.B.); Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5249, Laboratoire de Chimie et Biologie des Métaux, Grenoble, France (M.B.); and Department of Medicine, School of Clinical Sciences, Monash university and the Ritchie Centre, Hudson Institute of Medical Research, Clayton, Victoria, Australia (P.M.).</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Alfaidy, Nadia" sort="Alfaidy, Nadia" uniqKey="Alfaidy N" first="Nadia" last="Alfaidy">Nadia Alfaidy</name>
<affiliation><nlm:affiliation>From the Institut National de la Santé et de la Recherche Médicale, Grenoble, France (F.S., P.H., S.B., V.G., A.S., J.-J.F., N.A.); University Grenoble-Alpes, Grenoble, France (F.S., P.H., S.B., V.G., A.S., M.B., J.-J.F., N.A.); Commissariat à l'Energie Atomique (CEA), BIG (Biosciences Biotechnology Institute of Grenoble)-Biology of Cancer and Infection, Grenoble, France (F.S., P.H., S.B., V.G., A.S., M.B., J.-J.F., N.A.); Department of Obstetrics and Gynaecology, University Hospital of Grenoble, La Tronche, France (P.H.); Laboratoire d'Aide à la Procréation-CECOS, University Hospital of Grenoble, La Tronche, France (S.B.); Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5249, Laboratoire de Chimie et Biologie des Métaux, Grenoble, France (M.B.); and Department of Medicine, School of Clinical Sciences, Monash university and the Ritchie Centre, Hudson Institute of Medical Research, Clayton, Victoria, Australia (P.M.).</nlm:affiliation>
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<series><title level="j">Hypertension (Dallas, Tex. : 1979)</title>
<idno type="eISSN">1524-4563</idno>
<imprint><date when="2016" type="published">2016</date>
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<term>Blotting, Western</term>
<term>Disease Models, Animal</term>
<term>Female</term>
<term>Hypertension, Pregnancy-Induced (genetics)</term>
<term>Hypertension, Pregnancy-Induced (physiopathology)</term>
<term>Immunohistochemistry</term>
<term>Mice</term>
<term>Mice, Inbred Strains</term>
<term>Phenotype</term>
<term>Placenta (drug effects)</term>
<term>Placenta (pathology)</term>
<term>Pregnancy</term>
<term>Pregnancy Trimester, First</term>
<term>Pregnancy, Animal</term>
<term>Random Allocation</term>
<term>Real-Time Polymerase Chain Reaction (methods)</term>
<term>Receptors, G-Protein-Coupled (genetics)</term>
<term>Sensitivity and Specificity</term>
<term>Vascular Endothelial Growth Factor, Endocrine-Gland-Derived (blood)</term>
<term>Vascular Endothelial Growth Factor, Endocrine-Gland-Derived (pharmacology)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="blood" xml:lang="en"><term>Vascular Endothelial Growth Factor, Endocrine-Gland-Derived</term>
</keywords>
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</keywords>
<keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Placenta</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Hypertension, Pregnancy-Induced</term>
</keywords>
<keywords scheme="MESH" qualifier="methods" xml:lang="en"><term>Real-Time Polymerase Chain Reaction</term>
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<keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Placenta</term>
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<term>Biopsy, Needle</term>
<term>Blotting, Western</term>
<term>Disease Models, Animal</term>
<term>Female</term>
<term>Immunohistochemistry</term>
<term>Mice</term>
<term>Mice, Inbred Strains</term>
<term>Phenotype</term>
<term>Pregnancy</term>
<term>Pregnancy Trimester, First</term>
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<front><div type="abstract" xml:lang="en">Pregnancy-induced hypertension diseases are classified as gestational hypertension, preeclampsia, or eclampsia. The mechanisms of their development and prediction are still to be discovered. Endocrine gland-derived vascular endothelial growth factor (EG-VEGF) is an angiogenic factor secreted by the placenta during the first trimester of human pregnancy that was shown to control trophoblast invasion, to be upregulated by hypoxia, and to be abnormally elevated in pathological pregnancies complicated with preeclampsia and intrauterine growth restriction. These findings suggested that sustaining EG-VEGF levels beyond the first trimester of pregnancy may contribute to pregnancy-induced hypertension. To test this hypothesis, osmotic minipumps delivering EG-VEGF were implanted subcutaneously into gravid OF1 (Oncins France 1) mice on day 11.5 post coitus, which is equivalent to the end of the first trimester of human pregnancy. Mice were euthanized at 15.5 and 18.5 days post coitus to assess (1) litter size, placental, and fetal weights; (2) placental histology and function; (3) maternal blood pressure; (4) renal histology and function; and (5) circulating soluble fms-like tyrosine kinase 1 and soluble endoglin. Increased EG-VEGF levels caused significant defects in placental organization and function. Both increased hypoxia and decreased trophoblast invasion were observed. Treated mice had elevated circulating soluble fms-like tyrosine kinase 1 and soluble endoglin and developed gestational hypertension with dysregulated maternal kidney function. EG-VEGF effect on the kidney function was secondary to its effects on the placenta as similarly treated male mice had normal kidney functions. Altogether, these data provide a strong evidence to confirm that sustained EG-VEGF beyond the first trimester of pregnancy contributes to the development of pregnancy-induced hypertension.</div>
</front>
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<pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">27141059</PMID>
<DateCreated><Year>2016</Year>
<Month>06</Month>
<Day>10</Day>
</DateCreated>
<DateCompleted><Year>2017</Year>
<Month>07</Month>
<Day>19</Day>
</DateCompleted>
<DateRevised><Year>2017</Year>
<Month>07</Month>
<Day>19</Day>
</DateRevised>
<Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1524-4563</ISSN>
<JournalIssue CitedMedium="Internet"><Volume>68</Volume>
<Issue>1</Issue>
<PubDate><Year>2016</Year>
<Month>Jul</Month>
</PubDate>
</JournalIssue>
<Title>Hypertension (Dallas, Tex. : 1979)</Title>
<ISOAbbreviation>Hypertension</ISOAbbreviation>
</Journal>
<ArticleTitle>Sustained Endocrine Gland-Derived Vascular Endothelial Growth Factor Levels Beyond the First Trimester of Pregnancy Display Phenotypic and Functional Changes Associated With the Pathogenesis of Pregnancy-Induced Hypertension.</ArticleTitle>
<Pagination><MedlinePgn>148-56</MedlinePgn>
</Pagination>
<ELocationID EIdType="doi" ValidYN="Y">10.1161/HYPERTENSIONAHA.116.07442</ELocationID>
<Abstract><AbstractText>Pregnancy-induced hypertension diseases are classified as gestational hypertension, preeclampsia, or eclampsia. The mechanisms of their development and prediction are still to be discovered. Endocrine gland-derived vascular endothelial growth factor (EG-VEGF) is an angiogenic factor secreted by the placenta during the first trimester of human pregnancy that was shown to control trophoblast invasion, to be upregulated by hypoxia, and to be abnormally elevated in pathological pregnancies complicated with preeclampsia and intrauterine growth restriction. These findings suggested that sustaining EG-VEGF levels beyond the first trimester of pregnancy may contribute to pregnancy-induced hypertension. To test this hypothesis, osmotic minipumps delivering EG-VEGF were implanted subcutaneously into gravid OF1 (Oncins France 1) mice on day 11.5 post coitus, which is equivalent to the end of the first trimester of human pregnancy. Mice were euthanized at 15.5 and 18.5 days post coitus to assess (1) litter size, placental, and fetal weights; (2) placental histology and function; (3) maternal blood pressure; (4) renal histology and function; and (5) circulating soluble fms-like tyrosine kinase 1 and soluble endoglin. Increased EG-VEGF levels caused significant defects in placental organization and function. Both increased hypoxia and decreased trophoblast invasion were observed. Treated mice had elevated circulating soluble fms-like tyrosine kinase 1 and soluble endoglin and developed gestational hypertension with dysregulated maternal kidney function. EG-VEGF effect on the kidney function was secondary to its effects on the placenta as similarly treated male mice had normal kidney functions. Altogether, these data provide a strong evidence to confirm that sustained EG-VEGF beyond the first trimester of pregnancy contributes to the development of pregnancy-induced hypertension.</AbstractText>
<CopyrightInformation>© 2016 American Heart Association, Inc.</CopyrightInformation>
</Abstract>
<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Sergent</LastName>
<ForeName>Frédéric</ForeName>
<Initials>F</Initials>
<AffiliationInfo><Affiliation>From the Institut National de la Santé et de la Recherche Médicale, Grenoble, France (F.S., P.H., S.B., V.G., A.S., J.-J.F., N.A.); University Grenoble-Alpes, Grenoble, France (F.S., P.H., S.B., V.G., A.S., M.B., J.-J.F., N.A.); Commissariat à l'Energie Atomique (CEA), BIG (Biosciences Biotechnology Institute of Grenoble)-Biology of Cancer and Infection, Grenoble, France (F.S., P.H., S.B., V.G., A.S., M.B., J.-J.F., N.A.); Department of Obstetrics and Gynaecology, University Hospital of Grenoble, La Tronche, France (P.H.); Laboratoire d'Aide à la Procréation-CECOS, University Hospital of Grenoble, La Tronche, France (S.B.); Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5249, Laboratoire de Chimie et Biologie des Métaux, Grenoble, France (M.B.); and Department of Medicine, School of Clinical Sciences, Monash university and the Ritchie Centre, Hudson Institute of Medical Research, Clayton, Victoria, Australia (P.M.).</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Hoffmann</LastName>
<ForeName>Pascale</ForeName>
<Initials>P</Initials>
<AffiliationInfo><Affiliation>From the Institut National de la Santé et de la Recherche Médicale, Grenoble, France (F.S., P.H., S.B., V.G., A.S., J.-J.F., N.A.); University Grenoble-Alpes, Grenoble, France (F.S., P.H., S.B., V.G., A.S., M.B., J.-J.F., N.A.); Commissariat à l'Energie Atomique (CEA), BIG (Biosciences Biotechnology Institute of Grenoble)-Biology of Cancer and Infection, Grenoble, France (F.S., P.H., S.B., V.G., A.S., M.B., J.-J.F., N.A.); Department of Obstetrics and Gynaecology, University Hospital of Grenoble, La Tronche, France (P.H.); Laboratoire d'Aide à la Procréation-CECOS, University Hospital of Grenoble, La Tronche, France (S.B.); Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5249, Laboratoire de Chimie et Biologie des Métaux, Grenoble, France (M.B.); and Department of Medicine, School of Clinical Sciences, Monash university and the Ritchie Centre, Hudson Institute of Medical Research, Clayton, Victoria, Australia (P.M.).</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Brouillet</LastName>
<ForeName>Sophie</ForeName>
<Initials>S</Initials>
<AffiliationInfo><Affiliation>From the Institut National de la Santé et de la Recherche Médicale, Grenoble, France (F.S., P.H., S.B., V.G., A.S., J.-J.F., N.A.); University Grenoble-Alpes, Grenoble, France (F.S., P.H., S.B., V.G., A.S., M.B., J.-J.F., N.A.); Commissariat à l'Energie Atomique (CEA), BIG (Biosciences Biotechnology Institute of Grenoble)-Biology of Cancer and Infection, Grenoble, France (F.S., P.H., S.B., V.G., A.S., M.B., J.-J.F., N.A.); Department of Obstetrics and Gynaecology, University Hospital of Grenoble, La Tronche, France (P.H.); Laboratoire d'Aide à la Procréation-CECOS, University Hospital of Grenoble, La Tronche, France (S.B.); Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5249, Laboratoire de Chimie et Biologie des Métaux, Grenoble, France (M.B.); and Department of Medicine, School of Clinical Sciences, Monash university and the Ritchie Centre, Hudson Institute of Medical Research, Clayton, Victoria, Australia (P.M.).</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Garnier</LastName>
<ForeName>Vanessa</ForeName>
<Initials>V</Initials>
<AffiliationInfo><Affiliation>From the Institut National de la Santé et de la Recherche Médicale, Grenoble, France (F.S., P.H., S.B., V.G., A.S., J.-J.F., N.A.); University Grenoble-Alpes, Grenoble, France (F.S., P.H., S.B., V.G., A.S., M.B., J.-J.F., N.A.); Commissariat à l'Energie Atomique (CEA), BIG (Biosciences Biotechnology Institute of Grenoble)-Biology of Cancer and Infection, Grenoble, France (F.S., P.H., S.B., V.G., A.S., M.B., J.-J.F., N.A.); Department of Obstetrics and Gynaecology, University Hospital of Grenoble, La Tronche, France (P.H.); Laboratoire d'Aide à la Procréation-CECOS, University Hospital of Grenoble, La Tronche, France (S.B.); Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5249, Laboratoire de Chimie et Biologie des Métaux, Grenoble, France (M.B.); and Department of Medicine, School of Clinical Sciences, Monash university and the Ritchie Centre, Hudson Institute of Medical Research, Clayton, Victoria, Australia (P.M.).</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Salomon</LastName>
<ForeName>Aude</ForeName>
<Initials>A</Initials>
<AffiliationInfo><Affiliation>From the Institut National de la Santé et de la Recherche Médicale, Grenoble, France (F.S., P.H., S.B., V.G., A.S., J.-J.F., N.A.); University Grenoble-Alpes, Grenoble, France (F.S., P.H., S.B., V.G., A.S., M.B., J.-J.F., N.A.); Commissariat à l'Energie Atomique (CEA), BIG (Biosciences Biotechnology Institute of Grenoble)-Biology of Cancer and Infection, Grenoble, France (F.S., P.H., S.B., V.G., A.S., M.B., J.-J.F., N.A.); Department of Obstetrics and Gynaecology, University Hospital of Grenoble, La Tronche, France (P.H.); Laboratoire d'Aide à la Procréation-CECOS, University Hospital of Grenoble, La Tronche, France (S.B.); Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5249, Laboratoire de Chimie et Biologie des Métaux, Grenoble, France (M.B.); and Department of Medicine, School of Clinical Sciences, Monash university and the Ritchie Centre, Hudson Institute of Medical Research, Clayton, Victoria, Australia (P.M.).</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Murthi</LastName>
<ForeName>Padma</ForeName>
<Initials>P</Initials>
<AffiliationInfo><Affiliation>From the Institut National de la Santé et de la Recherche Médicale, Grenoble, France (F.S., P.H., S.B., V.G., A.S., J.-J.F., N.A.); University Grenoble-Alpes, Grenoble, France (F.S., P.H., S.B., V.G., A.S., M.B., J.-J.F., N.A.); Commissariat à l'Energie Atomique (CEA), BIG (Biosciences Biotechnology Institute of Grenoble)-Biology of Cancer and Infection, Grenoble, France (F.S., P.H., S.B., V.G., A.S., M.B., J.-J.F., N.A.); Department of Obstetrics and Gynaecology, University Hospital of Grenoble, La Tronche, France (P.H.); Laboratoire d'Aide à la Procréation-CECOS, University Hospital of Grenoble, La Tronche, France (S.B.); Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5249, Laboratoire de Chimie et Biologie des Métaux, Grenoble, France (M.B.); and Department of Medicine, School of Clinical Sciences, Monash university and the Ritchie Centre, Hudson Institute of Medical Research, Clayton, Victoria, Australia (P.M.).</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Benharouga</LastName>
<ForeName>Mohamed</ForeName>
<Initials>M</Initials>
<AffiliationInfo><Affiliation>From the Institut National de la Santé et de la Recherche Médicale, Grenoble, France (F.S., P.H., S.B., V.G., A.S., J.-J.F., N.A.); University Grenoble-Alpes, Grenoble, France (F.S., P.H., S.B., V.G., A.S., M.B., J.-J.F., N.A.); Commissariat à l'Energie Atomique (CEA), BIG (Biosciences Biotechnology Institute of Grenoble)-Biology of Cancer and Infection, Grenoble, France (F.S., P.H., S.B., V.G., A.S., M.B., J.-J.F., N.A.); Department of Obstetrics and Gynaecology, University Hospital of Grenoble, La Tronche, France (P.H.); Laboratoire d'Aide à la Procréation-CECOS, University Hospital of Grenoble, La Tronche, France (S.B.); Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5249, Laboratoire de Chimie et Biologie des Métaux, Grenoble, France (M.B.); and Department of Medicine, School of Clinical Sciences, Monash university and the Ritchie Centre, Hudson Institute of Medical Research, Clayton, Victoria, Australia (P.M.).</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Feige</LastName>
<ForeName>Jean-Jacques</ForeName>
<Initials>JJ</Initials>
<AffiliationInfo><Affiliation>From the Institut National de la Santé et de la Recherche Médicale, Grenoble, France (F.S., P.H., S.B., V.G., A.S., J.-J.F., N.A.); University Grenoble-Alpes, Grenoble, France (F.S., P.H., S.B., V.G., A.S., M.B., J.-J.F., N.A.); Commissariat à l'Energie Atomique (CEA), BIG (Biosciences Biotechnology Institute of Grenoble)-Biology of Cancer and Infection, Grenoble, France (F.S., P.H., S.B., V.G., A.S., M.B., J.-J.F., N.A.); Department of Obstetrics and Gynaecology, University Hospital of Grenoble, La Tronche, France (P.H.); Laboratoire d'Aide à la Procréation-CECOS, University Hospital of Grenoble, La Tronche, France (S.B.); Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5249, Laboratoire de Chimie et Biologie des Métaux, Grenoble, France (M.B.); and Department of Medicine, School of Clinical Sciences, Monash university and the Ritchie Centre, Hudson Institute of Medical Research, Clayton, Victoria, Australia (P.M.).</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Alfaidy</LastName>
<ForeName>Nadia</ForeName>
<Initials>N</Initials>
<AffiliationInfo><Affiliation>From the Institut National de la Santé et de la Recherche Médicale, Grenoble, France (F.S., P.H., S.B., V.G., A.S., J.-J.F., N.A.); University Grenoble-Alpes, Grenoble, France (F.S., P.H., S.B., V.G., A.S., M.B., J.-J.F., N.A.); Commissariat à l'Energie Atomique (CEA), BIG (Biosciences Biotechnology Institute of Grenoble)-Biology of Cancer and Infection, Grenoble, France (F.S., P.H., S.B., V.G., A.S., M.B., J.-J.F., N.A.); Department of Obstetrics and Gynaecology, University Hospital of Grenoble, La Tronche, France (P.H.); Laboratoire d'Aide à la Procréation-CECOS, University Hospital of Grenoble, La Tronche, France (S.B.); Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5249, Laboratoire de Chimie et Biologie des Métaux, Grenoble, France (M.B.); and Department of Medicine, School of Clinical Sciences, Monash university and the Ritchie Centre, Hudson Institute of Medical Research, Clayton, Victoria, Australia (P.M.).</Affiliation>
</AffiliationInfo>
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<Language>eng</Language>
<PublicationTypeList><PublicationType UI="D003160">Comparative Study</PublicationType>
<PublicationType UI="D016428">Journal Article</PublicationType>
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<Month>05</Month>
<Day>02</Day>
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<ChemicalList><Chemical><RegistryNumber>0</RegistryNumber>
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</MeshHeading>
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</MeshHeading>
<MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName>
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</MeshHeading>
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</MeshHeading>
<MeshHeading><DescriptorName UI="D011270" MajorTopicYN="Y">Pregnancy, Animal</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D011897" MajorTopicYN="N">Random Allocation</DescriptorName>
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<MeshHeading><DescriptorName UI="D060888" MajorTopicYN="N">Real-Time Polymerase Chain Reaction</DescriptorName>
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</MeshHeading>
<MeshHeading><DescriptorName UI="D043562" MajorTopicYN="N">Receptors, G-Protein-Coupled</DescriptorName>
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<QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName>
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</MeshHeadingList>
<KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">endocrine gland-derived endothelial growth factor</Keyword>
<Keyword MajorTopicYN="N">hypertension</Keyword>
<Keyword MajorTopicYN="N">preeclampsia</Keyword>
<Keyword MajorTopicYN="N">pregnancy-induced hypertension</Keyword>
<Keyword MajorTopicYN="N">prokineticin 1</Keyword>
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<Month>03</Month>
<Day>03</Day>
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<Month>04</Month>
<Day>01</Day>
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