Gestational diabetes impacts fetal precursor cell responses with potential consequences for offspring

Stem Cells Translational Medicine

Gemma Llauradó¹  Mónica Ballesteros²  Albert Guarque²  Ramón Bosch²  Carlos López²  Laia Martínez‐Guasch³  Francisco Algaba‐Chueca³  Sonia Fernández‐Veledo³  Ana Megía³  Carolina Serena³  Joan Vendrell³  Cristina Gutiérrez³  Miriam Ejarque³  Elsa Maymó‐Masip³ 

[1] CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM)‐Instituto de Salud Carlos III Madrid Spain;Institut d'Investigació Sanitària Pere Virgili (IISPV) Tarragona Spain;Servei d'Endocrinologia i Nutrició i Unitat de Recerca Hospital Universitari de Tarragona Joan XXIII Tarragona Spain;

关键词: fetal precursors;    gestational diabetes;    offspring;    placenta;    programming;    stem cells;   

DOI  :  10.1002/sctm.19-0242

来源: DOAJ

【 摘 要 】

Abstract 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.

【 授权许可】

Unknown