An EG-VEGF-Dependent Decrease in Homeobox Gene NKX3.1 Contributes to Cytotrophoblast Dysfunction: A Possible Mechanism in Human Fetal Growth Restriction
Identifieur interne : 003183 ( Main/Exploration ); précédent : 003182; suivant : 003184An EG-VEGF-Dependent Decrease in Homeobox Gene NKX3.1 Contributes to Cytotrophoblast Dysfunction: A Possible Mechanism in Human Fetal Growth Restriction
Auteurs : Padma Murthi [Australie] ; Sophie Brouillet [France] ; Anita Pratt [Australie] ; Anthony Borg [Australie] ; Bill Kalionis [Australie] ; Frederic Goffin [Belgique] ; Vassilis Tsatsaris [France] ; Carine Munaut [Belgique] ; Jean-Jacques Feige [France] ; Mohamed Benharouga [France] ; Thierry Fournier [France] ; Nadia Alfaidy [France]Source :
- Molecular Medicine [ 1076-1551 ] ; 2015.
Abstract
Idiopathic fetal growth restriction (FGR) is frequently associated with placental insufficiency. Previous reports have provided evidence that endocrine gland–derived vascular endothelial growth factor (EG-VEGF), a placental secreted protein, is expressed during the first trimester of pregnancy, controls both trophoblast proliferation and invasion, and its increased expression is associated with human FGR. In this study, we hypothesize that EG-VEGF-dependent changes in placental homeobox gene expressions contribute to trophoblast dysfunction in idiopathic FGR. The changes in EG-VEGF-dependent homeobox gene expressions were determined using a homeobox gene cDNA array on placental explants of 8–12 wks gestation after stimulation with EG-VEGF
Url:
DOI: 10.2119/molmed.2015.00071
PubMed: 26208047
PubMed Central: 4749495
Affiliations:
- Australie, Belgique, France
- Auvergne-Rhône-Alpes, Province de Liège, Rhône-Alpes, Région wallonne, Île-de-France
- Grenoble, Liège, Paris
- Université Grenoble-Alpes, Université de Liège
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Women’s Hospital, Victoria, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Perinatal Medicine Pregnancy Research Centre, The Royal Women’s Hospital and The University of Melbourne Department of Obstetrics and Gynaecology, The Royal Women’s Hospital, Victoria</wicri:regionArea><wicri:noRegion>Victoria</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="af2-15_071_murthi">Department of Medicine, Monash University, Victoria, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Medicine, Monash University, Victoria</wicri:regionArea><wicri:noRegion>Victoria</wicri:noRegion></affiliation></author><author><name sortKey="Brouillet, Sophie" sort="Brouillet, Sophie" uniqKey="Brouillet S" first="Sophie" last="Brouillet">Sophie Brouillet</name><affiliation wicri:level="3"><nlm:aff id="af3-15_071_murthi">Institut National de la Santé et de la Recherche Médicale, Unité 1036, Grenoble, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Santé et de la Recherche Médicale, Unité 1036, Grenoble</wicri:regionArea><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Grenoble</settlement></placeName></affiliation><affiliation wicri:level="4"><nlm:aff id="af4-15_071_murthi">Université Grenoble-Alpes, Grenoble, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Université Grenoble-Alpes, Grenoble</wicri:regionArea><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Grenoble</settlement><settlement type="city">Grenoble</settlement></placeName><orgName type="university">Université Grenoble-Alpes</orgName></affiliation><affiliation wicri:level="3"><nlm:aff id="af5-15_071_murthi">Commissariat à L’Energie Atomique (CEA), iRTSV–Biology of Cancer and Infection, Grenoble, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Commissariat à L’Energie Atomique (CEA), iRTSV–Biology of Cancer and Infection, Grenoble</wicri:regionArea><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Grenoble</settlement></placeName></affiliation><affiliation wicri:level="1"><nlm:aff id="af6-15_071_murthi">Centre Hospitalier Universitaire de Grenoble, Hôpital Couple-Enfant, Centre Clinique et Biologique d’Assistance Médicale à la Procréation, La Tronche, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Centre Hospitalier Universitaire de Grenoble, Hôpital Couple-Enfant, Centre Clinique et Biologique d’Assistance Médicale à la Procréation, La Tronche</wicri:regionArea><wicri:noRegion>La Tronche</wicri:noRegion><wicri:noRegion>La Tronche</wicri:noRegion></affiliation></author><author><name sortKey="Pratt, Anita" sort="Pratt, Anita" uniqKey="Pratt A" first="Anita" last="Pratt">Anita Pratt</name><affiliation wicri:level="1"><nlm:aff id="af1-15_071_murthi">Department of Perinatal Medicine Pregnancy Research Centre, The Royal Women’s Hospital and The University of Melbourne Department of Obstetrics and Gynaecology, The Royal Women’s Hospital, Victoria, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Perinatal Medicine Pregnancy Research Centre, The Royal Women’s Hospital and The University of Melbourne Department of Obstetrics and Gynaecology, The Royal Women’s Hospital, Victoria</wicri:regionArea><wicri:noRegion>Victoria</wicri:noRegion></affiliation></author><author><name sortKey="Borg, Anthony" sort="Borg, Anthony" uniqKey="Borg A" first="Anthony" last="Borg">Anthony Borg</name><affiliation wicri:level="1"><nlm:aff id="af1-15_071_murthi">Department of Perinatal Medicine Pregnancy Research Centre, The Royal Women’s Hospital and The University of Melbourne Department of Obstetrics and Gynaecology, The Royal Women’s Hospital, Victoria, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Perinatal Medicine Pregnancy Research Centre, The Royal Women’s Hospital and The University of Melbourne Department of Obstetrics and Gynaecology, The Royal Women’s Hospital, Victoria</wicri:regionArea><wicri:noRegion>Victoria</wicri:noRegion></affiliation></author><author><name sortKey="Kalionis, Bill" sort="Kalionis, Bill" uniqKey="Kalionis B" first="Bill" last="Kalionis">Bill Kalionis</name><affiliation wicri:level="1"><nlm:aff id="af1-15_071_murthi">Department of Perinatal Medicine Pregnancy Research Centre, The Royal Women’s Hospital and The University of Melbourne Department of Obstetrics and Gynaecology, The Royal Women’s Hospital, Victoria, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Perinatal Medicine Pregnancy Research Centre, The Royal Women’s Hospital and The University of Melbourne Department of Obstetrics and Gynaecology, The Royal Women’s Hospital, Victoria</wicri:regionArea><wicri:noRegion>Victoria</wicri:noRegion></affiliation></author><author><name sortKey="Goffin, Frederic" sort="Goffin, Frederic" uniqKey="Goffin F" first="Frederic" last="Goffin">Frederic Goffin</name><affiliation wicri:level="4"><nlm:aff id="af7-15_071_murthi">Laboratory of Tumor and Developmental Biology, University of Liège, Belgium</nlm:aff><country xml:lang="fr">Belgique</country><wicri:regionArea>Laboratory of Tumor and Developmental Biology, University of Liège</wicri:regionArea><placeName><settlement type="city">Liège</settlement><region type="region" nuts="1">Région wallonne</region><region type="province" nuts="1">Province de Liège</region></placeName><orgName type="university">Université de Liège</orgName></affiliation></author><author><name sortKey="Tsatsaris, Vassilis" sort="Tsatsaris, Vassilis" uniqKey="Tsatsaris V" first="Vassilis" last="Tsatsaris">Vassilis Tsatsaris</name><affiliation wicri:level="3"><nlm:aff id="af8-15_071_murthi">Department of Obstetrics and Gynecology, Hôpital Cochin, Maternité Port-Royal, Université Rene Descartes, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Department of Obstetrics and Gynecology, Hôpital Cochin, Maternité Port-Royal, Université Rene Descartes, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Munaut, Carine" sort="Munaut, Carine" uniqKey="Munaut C" first="Carine" last="Munaut">Carine Munaut</name><affiliation wicri:level="4"><nlm:aff id="af7-15_071_murthi">Laboratory of Tumor and Developmental Biology, University of Liège, Belgium</nlm:aff><country xml:lang="fr">Belgique</country><wicri:regionArea>Laboratory of Tumor and Developmental Biology, University of Liège</wicri:regionArea><placeName><settlement type="city">Liège</settlement><region type="region" nuts="1">Région wallonne</region><region type="province" nuts="1">Province de Liège</region></placeName><orgName type="university">Université de Liège</orgName></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 wicri:level="3"><nlm:aff id="af3-15_071_murthi">Institut National de la Santé et de la Recherche Médicale, Unité 1036, Grenoble, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Santé et de la Recherche Médicale, Unité 1036, Grenoble</wicri:regionArea><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Grenoble</settlement></placeName></affiliation><affiliation wicri:level="4"><nlm:aff id="af4-15_071_murthi">Université Grenoble-Alpes, Grenoble, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Université Grenoble-Alpes, Grenoble</wicri:regionArea><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Grenoble</settlement><settlement type="city">Grenoble</settlement></placeName><orgName type="university">Université Grenoble-Alpes</orgName></affiliation><affiliation wicri:level="3"><nlm:aff id="af5-15_071_murthi">Commissariat à L’Energie Atomique (CEA), iRTSV–Biology of Cancer and Infection, Grenoble, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Commissariat à L’Energie Atomique (CEA), iRTSV–Biology of Cancer and Infection, Grenoble</wicri:regionArea><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Grenoble</settlement></placeName></affiliation></author><author><name sortKey="Benharouga, Mohamed" sort="Benharouga, Mohamed" uniqKey="Benharouga M" first="Mohamed" last="Benharouga">Mohamed Benharouga</name><affiliation wicri:level="3"><nlm:aff id="af9-15_071_murthi">Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5249, Laboratoire de Chimie et Biologie des Métaux, Grenoble, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5249, Laboratoire de Chimie et Biologie des Métaux, Grenoble</wicri:regionArea><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Grenoble</settlement></placeName></affiliation></author><author><name sortKey="Fournier, Thierry" sort="Fournier, Thierry" uniqKey="Fournier T" first="Thierry" last="Fournier">Thierry Fournier</name><affiliation wicri:level="3"><nlm:aff id="af10-15_071_murthi">INSERM, U1139; Universite Paris Descartes, UMR-S1139; and PremUp Foundation, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>INSERM, U1139; Universite Paris Descartes, UMR-S1139; and PremUp Foundation, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Alfaidy, Nadia" sort="Alfaidy, Nadia" uniqKey="Alfaidy N" first="Nadia" last="Alfaidy">Nadia Alfaidy</name><affiliation wicri:level="3"><nlm:aff id="af3-15_071_murthi">Institut National de la Santé et de la Recherche Médicale, Unité 1036, Grenoble, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Santé et de la Recherche Médicale, Unité 1036, Grenoble</wicri:regionArea><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Grenoble</settlement></placeName></affiliation><affiliation wicri:level="4"><nlm:aff id="af4-15_071_murthi">Université Grenoble-Alpes, Grenoble, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Université Grenoble-Alpes, Grenoble</wicri:regionArea><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Grenoble</settlement><settlement type="city">Grenoble</settlement></placeName><orgName type="university">Université Grenoble-Alpes</orgName></affiliation><affiliation wicri:level="3"><nlm:aff id="af5-15_071_murthi">Commissariat à L’Energie Atomique (CEA), iRTSV–Biology of Cancer and Infection, Grenoble, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Commissariat à L’Energie Atomique (CEA), iRTSV–Biology of Cancer and Infection, Grenoble</wicri:regionArea><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Grenoble</settlement></placeName></affiliation></author></analytic><series><title level="j">Molecular Medicine</title><idno type="ISSN">1076-1551</idno><idno type="eISSN">1528-3658</idno><imprint><date when="2015">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Idiopathic fetal growth restriction (FGR) is frequently associated with placental insufficiency. Previous reports have provided evidence that endocrine gland–derived vascular endothelial growth factor (EG-VEGF), a placental secreted protein, is expressed during the first trimester of pregnancy, controls both trophoblast proliferation and invasion, and its increased expression is associated with human FGR. In this study, we hypothesize that EG-VEGF-dependent changes in placental homeobox gene expressions contribute to trophoblast dysfunction in idiopathic FGR. The changes in EG-VEGF-dependent homeobox gene expressions were determined using a homeobox gene cDNA array on placental explants of 8–12 wks gestation after stimulation with EG-VEGF <italic>in vitro</italic> for 24 h. The homeobox gene array identified a greater-than-five-fold increase in <italic>HOXA9</italic>, <italic>HOXC8</italic>, <italic>HOXC10</italic>, <italic>HOXD1</italic>, <italic>HOXD8</italic>, <italic>HOXD9</italic> and <italic>HOXD11</italic>, while <italic>NKX 3.1</italic> showed a greater-than-two-fold decrease in mRNA expression compared with untreated controls. Homeobox gene <italic>NKX3.1</italic> was selected as a candidate because it is a downstream target of EG-VEGF and its expression and functional roles are largely unknown in control and idiopathic FGR-affected placentae. Real-time PCR and immunoblotting showed a significant decrease in <italic>NKX3.1</italic> mRNA and protein levels, respectively, in placentae from FGR compared with control pregnancies. Gene inactivation <italic>in vitro</italic> using short-interference RNA specific for <italic>NKX3.1</italic> demonstrated an increase in BeWo cell differentiation and a decrease in HTR-8/SVneo proliferation. We conclude that the decreased expression of homeobox gene <italic>NKX3.1</italic> downstream of EG-VEGF may contribute to the trophoblast dysfunction associated with idiopathic FGR pregnancies.</p></div></front></TEI><affiliations><list><country><li>Australie</li><li>Belgique</li><li>France</li></country><region><li>Auvergne-Rhône-Alpes</li><li>Province de Liège</li><li>Rhône-Alpes</li><li>Région wallonne</li><li>Île-de-France</li></region><settlement><li>Grenoble</li><li>Liège</li><li>Paris</li></settlement><orgName><li>Université Grenoble-Alpes</li><li>Université de Liège</li></orgName></list><tree><country name="Australie"><noRegion><name sortKey="Murthi, Padma" sort="Murthi, Padma" uniqKey="Murthi P" first="Padma" last="Murthi">Padma Murthi</name></noRegion><name sortKey="Borg, Anthony" sort="Borg, Anthony" uniqKey="Borg A" first="Anthony" last="Borg">Anthony Borg</name><name sortKey="Kalionis, Bill" sort="Kalionis, Bill" uniqKey="Kalionis B" first="Bill" last="Kalionis">Bill Kalionis</name><name sortKey="Murthi, Padma" sort="Murthi, Padma" uniqKey="Murthi P" first="Padma" last="Murthi">Padma Murthi</name><name sortKey="Pratt, Anita" sort="Pratt, Anita" uniqKey="Pratt A" first="Anita" last="Pratt">Anita Pratt</name></country><country name="France"><region name="Auvergne-Rhône-Alpes"><name sortKey="Brouillet, Sophie" sort="Brouillet, Sophie" uniqKey="Brouillet S" first="Sophie" last="Brouillet">Sophie Brouillet</name></region><name sortKey="Alfaidy, Nadia" sort="Alfaidy, Nadia" uniqKey="Alfaidy N" first="Nadia" last="Alfaidy">Nadia Alfaidy</name><name sortKey="Alfaidy, Nadia" sort="Alfaidy, Nadia" uniqKey="Alfaidy N" first="Nadia" last="Alfaidy">Nadia Alfaidy</name><name sortKey="Alfaidy, Nadia" sort="Alfaidy, Nadia" uniqKey="Alfaidy N" first="Nadia" last="Alfaidy">Nadia Alfaidy</name><name sortKey="Benharouga, Mohamed" sort="Benharouga, Mohamed" uniqKey="Benharouga M" first="Mohamed" last="Benharouga">Mohamed Benharouga</name><name sortKey="Brouillet, Sophie" sort="Brouillet, Sophie" uniqKey="Brouillet S" first="Sophie" last="Brouillet">Sophie Brouillet</name><name sortKey="Brouillet, Sophie" sort="Brouillet, Sophie" uniqKey="Brouillet S" first="Sophie" last="Brouillet">Sophie Brouillet</name><name sortKey="Brouillet, Sophie" sort="Brouillet, Sophie" uniqKey="Brouillet S" first="Sophie" last="Brouillet">Sophie Brouillet</name><name sortKey="Feige, Jean Jacques" sort="Feige, Jean Jacques" uniqKey="Feige J" first="Jean-Jacques" last="Feige">Jean-Jacques Feige</name><name sortKey="Feige, Jean Jacques" sort="Feige, Jean Jacques" uniqKey="Feige J" first="Jean-Jacques" last="Feige">Jean-Jacques Feige</name><name sortKey="Feige, Jean Jacques" sort="Feige, Jean Jacques" uniqKey="Feige J" first="Jean-Jacques" last="Feige">Jean-Jacques Feige</name><name sortKey="Fournier, Thierry" sort="Fournier, Thierry" uniqKey="Fournier T" first="Thierry" last="Fournier">Thierry Fournier</name><name sortKey="Tsatsaris, Vassilis" sort="Tsatsaris, Vassilis" uniqKey="Tsatsaris V" first="Vassilis" last="Tsatsaris">Vassilis Tsatsaris</name></country><country name="Belgique"><region name="Région wallonne"><name sortKey="Goffin, Frederic" sort="Goffin, Frederic" uniqKey="Goffin F" first="Frederic" last="Goffin">Frederic Goffin</name></region><name sortKey="Munaut, Carine" sort="Munaut, Carine" uniqKey="Munaut C" first="Carine" last="Munaut">Carine Munaut</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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