Author, as appears in the article.: Algaba-Chueca F., Maymó-Masip E., Ejarque M., Ballesteros M., Llauradó G., López C., Guarque A., Serena C., Martínez-Guasch L., Gutiérrez C., Bosch R., Vendrell J., Megía A., Fernández-Veledo S.

Department: Bioquímica i Biotecnologia Ciències Mèdiques Bàsiques Medicina i Cirurgia

URV's Author/s: Fernandez Veledo, Sonia / Lopez Pablo, Carlos / Maymo Masip, Elsa / Megía Colet, Ana / Vendrell Ortega, Juan José

Keywords: Stem cells Programming Placenta Offspring Obesity Metabolism Mesenchymal stromal cells Mellitus Insulin-resistance Glucose Gestational diabetes Fetal precursors Differentiation Alters programming placenta offspring gestational diabetes fetal precursors

Abstract: © 2019 The Authors. STEM CELLS TRANSLATIONAL MEDICINE published by Wiley Periodicals, Inc. on behalf of AlphaMed Press Fetal programming has been proposed as a key mechanism underlying the association between intrauterine exposure to maternal diabetes and negative health outcomes in offspring. To determine whether gestational diabetes mellitus (GDM) might leave an imprint in fetal precursors of the amniotic membrane and whether it might be related to adverse outcomes in offspring, a prospective case-control study was conducted, in which amniotic mesenchymal stem cells (AMSCs) and resident macrophages were isolated from pregnant patients, with either GDM or normal glucose tolerance, scheduled for cesarean section. After characterization, functional characteristics of AMSCs were analyzed and correlated with anthropometrical and clinical variables from both mother and offspring. GDM-derived AMSCs displayed an impaired proliferation and osteogenic potential when compared with control cells, accompanied by superior invasive and chemotactic capacity. The expression of genes involved in the inflammatory response (TNFα, MCP-1, CD40, and CTSS) was upregulated in GDM-derived AMSCs, whereas anti-inflammatory IL-33 was downregulated. Macrophages isolated from the amniotic membrane of GDM mothers consistently showed higher expression of MCP-1 as well. In vitro studies in which AMSCs from healthy control women were exposed to hyperglycemia, hyperinsulinemia, and palmitic acid confirmed these results. Finally, genes involved in the inflammatory response were associated with maternal insulin sensitivity and prepregnancy body mass index, as well as with fetal metabolic parameters. These results suggest that the GDM environment could program stem cells and subsequently favor metabolic dysfunction later in life. Fetal adaptive programming in the setting of GDM might have a direct negative impact on insulin resistance of offspring.

Thematic Areas: Medicine (miscellaneous) Medicine (all) Medicina ii Medicina i General medicine Developmental biology Ciências biológicas iii Ciências biológicas ii Cell biology Cell & tissue engineering

licence for use: https://creativecommons.org/licenses/by/3.0/es/

ISSN: 21576564

Author's mail: sonia.fernandez@urv.cat elsa.maymo@urv.cat carlos.lopez@urv.cat juanjose.vendrell@urv.cat ana.megia@urv.cat

Author identifier: 0000-0003-2906-3788 0000-0002-9133-3120 0000-0003-1248-3065 0000-0002-6994-6115 0000-0002-5101-9452

Record's date: 2023-02-18

Papper version: info:eu-repo/semantics/publishedVersion

Link to the original source: https://stemcellsjournals.onlinelibrary.wiley.com/doi/full/10.1002/sctm.19-0242

Licence document URL: http://repositori.urv.cat/ca/proteccio-de-dades/

Papper original source: Stem Cells Translational Medicine. 9 (3): 351-363

APA: Algaba-Chueca F., Maymó-Masip E., Ejarque M., Ballesteros M., Llauradó G., López C., Guarque A., Serena C., Martínez-Guasch L., Gutiérrez C., Bosch R. (2020). Gestational diabetes impacts fetal precursor cell responses with potential consequences for offspring. Stem Cells Translational Medicine, 9(3), 351-363. DOI: 10.1002/sctm.19-0242

Article's DOI: 10.1002/sctm.19-0242

Entity: Universitat Rovira i Virgili

Journal publication year: 2020

Publication Type: Journal Publications