Study of Human T21 Placenta Suggests a Potential Role of Mesenchymal Spondin-2 in Placental Vascular Development
| Autor: | Benoît Sarazin, Josette Badet, Danièle Evain-Brion, Fabien Guimiot, Padma Murthi, Pascale Gerbaud, Jean Guibourdenche, Guillaume Pidoux |
|---|---|
| Přispěvatelé: | Physiopathologie et Pharmacotoxicologie Placentaire Humaine (U1139), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Signalisation et physiopathologie cardiovasculaire (UMRS1180), Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Obstetrics and Gynaecology [Melbourne], Melbourne Medical School [Melbourne], Faculty of Medicine, Dentistry and Health Sciences [Melbourne], University of Melbourne-University of Melbourne-Faculty of Medicine, Dentistry and Health Sciences [Melbourne], University of Melbourne-University of Melbourne, University of Melbourne, Monash University [Clayton], Hudson Institute of Medical Research [Clayton], Université Paris Descartes - Faculté de Pharmacie de Paris (UPD5 Pharmacie), Université Paris Descartes - Paris 5 (UPD5), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Fondation PremUp, CHU Robert Debré, Proteomic Solutions [Saint-Marcel], Pidoux, Guillaume |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Angiogenesis Placenta Neovascularization Physiologic [SDV.BC]Life Sciences [q-bio]/Cellular Biology [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC] Biology [SDV.MHEP.GEO]Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics Extracellular matrix 03 medical and health sciences Paracrine signalling 0302 clinical medicine Endocrinology Pregnancy Internal medicine medicine [SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC] Humans [SDV.BC] Life Sciences [q-bio]/Cellular Biology [SDV.BDLR] Life Sciences [q-bio]/Reproductive Biology Fetus Extracellular Matrix Proteins [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology Mesenchymal stem cell Placentation [SDV.BDLR]Life Sciences [q-bio]/Reproductive Biology Cell biology Endostatins Neoplasm Proteins Crosstalk (biology) [SDV.MHEP.GEO] Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis Case-Control Studies Intercellular Signaling Peptides and Proteins Female Down Syndrome [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology |
| Zdroj: | Endocrinology Endocrinology, Endocrine Society, 2019, 160 (3), pp.684-698. ⟨10.1210/en.2018-00826⟩ |
| ISSN: | 0013-7227 |
| DOI: | 10.1210/en.2018-00826⟩ |
| Popis: | Placental development is particularly altered in trisomy of chromosome 21 (T21)–affected pregnancies. We previously described in T21-affected placentae an abnormal paracrine crosstalk between the villus mesenchymal core and villus trophoblasts. T21-affected placentae are known to be characterized by their hypovascularity. However, the causes of this anomaly remain not fully elucidated. Therefore, the hypothesis of an abnormal paracrine crosstalk between fetal mesenchymal core and placental endothelial cells (PLECs) was evocated. Villus mesenchymal cells from control (CMCs) and T21 placentae (T21MCs) were isolated and grown in culture to allow their characterization and collection of conditioned media for functional analyses (CMC-CM and T21MC-CM, respectively). Interestingly, PLEC proliferation and branching ability were less stimulated by T21MC-CM than by CMC-CM. Protein array analysis identified secreted proangiogenic growth factors in CMC-CM, which were reduced in T21MC-CM. Combined mass spectrometry and biochemical analysis identified spondin-2 as a factor decreased in T21MC-CM compared with CMC-CM. We found that exogenous spondin-2 stimulated PLEC proliferation and established that T21MC-CM supplemented with spondin-2 recovered conditioned media ability to induce PLEC proliferation and angiogenesis. Hence, this study demonstrates a crosstalk between villus mesenchymal and fetal endothelial cells, in which spondin-2 secreted from mesenchymal cells plays a central role in placental vascular functions. Furthermore, our results also suggest that a reduction in spondin-2 secretion may contribute to the pathogenesis of T21 placental hypovascularity. |
| Databáze: | OpenAIRE |
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