Ursula Hiden, Dr.rer.nat.:

Programming function of fetal endothelial cells by maternal metabolism

Department of Obstetrics and Gynecology, Medical University of Graz, Auenbruggerplatz 14, A-8036 Graz;
phone: +43-316-385 17837, fax: +43-316-385 14197,  e-mail
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Endothelial progenitor cells, gestational diabetes mellitus, programming, endothelial function, DNA methylation

Research interest:

Metabolic derangements such as diabetes affect cellular functions, and endothelial dysfunction is a well-known consequence of obesity and diabetes. I am interested in the effect of maternal metabolic derangements in pregnancy, such as gestational diabetes mellitus (GDM), on development and function of fetal and placental endothelium.

Accumulating evidence demonstrates that the intrauterine environment determines fetal development and susceptibility to diseases later in life, a process referred to as programming. For instance, maternal metabolic derangements increase the offspring's risk for metabolic and cardiovascular diseases in later life (1). This has raised interest in the process of vascular development and its programming by adverse maternal environments. Changes in DNA methylation are the main mechanism underlying the permanent effect of programming (2). Elucidating the mechanisms and functional consequences of programming endothelial function in utero by maternal environment has become a particular focus of my research. Thus, we recently identified DNA methylation differences in feto-placental endothelial cells after maternal GDM that were paralleled by altered endothelial function (Cvitic et al., unpublished).

Endothelial colony forming cells (ECFCs) are circulating endothelial progenitor cells that repair endothelial damage and participate in angiogenesis. Due to major angiogenic and vascular remodelling processes during fetal development and during the perinatal period, ECFCs are highly abundant in cord blood of newborns. We and others have identified functional changes of fetal ECFCs isolated form cord blood, when mothers had GDM (Leopold et al., unpublished; 3). These included reduced proliferation, migration and wound healing. Not only metabolic environment determines endothelial function. Endothelial function also differs between males and females, and, besides hormones, genetics plays a role. Indeed, we have demonstrated sex specific transcriptome in placental endothelial cells (4), and have identified sex-dependent functional changes of placental endothelial cells after exposure to maternal GDM (Strutz et al., unpublished).


Fig. 1: Sprouting of spheroids formed by ECFCs that were isolated after normal (A) or GDM (B) pregnancy. The spheroids formed in hanging drops 16 hours after seeding of the cells. GDM derived ECFCs show less sprouting that control cells.


  1. Barker DJ: The origins of the developmental origins theory. J Intern Med, 2007; 261(5):412–417.
  2. Reynolds RM, Jacobsen GH, Drake AJ: What is the evidence in humans that DNA methylation changes link events in utero and later life disease? Clin Endocrinol (Oxf), 2013; 78(6):814–822.
  3. Ingram DA, Lien IZ, Mead LE, Estes M, Prater DN, Derr-Yellin E, DiMeglio LA, Haneline LS: In vitro hyperglycemia or a diabetic intrauterine environment reduces neonatal endothelial colony-forming cell numbers and function. Diabetes, 2008; 57(3):724–731.
  4. Cvitic S, Longtine MS, Hackl H, Wagner K, Nelson MD, Desoye G, Hiden U: The human placental sexome differs between trophoblast epithelium and villous vessel endothelium. PLoS One, 2013; 8(10):e79233.

Collaborations within the DP-iDP:

  • M. Gauster will train the student in physiology and morphology of the placenta.
  • Á. Heinemann will support the student in adhesion assays.

Collaborating research groups where PhD students could perform their research stay abroad:

  • R. Saffery (Cancer and Disease Epigenetics, Murdoch Children's Research Institute, Royal Children's Hospital, Melbourne, Australia) is an expert in the field of epigenetics and programming by DNA methylation.

Know-how and infrastructure of the research group:

The laboratory has long standing expertise in endothelial cell culture, characterisation and investigating endothelial function. The functional assays include 2D and 3D angiogenesis assays, i.e. Matrigel assays, spheroid sprouting assays, and fibrin assays, analysis of barrier function (ECIS and transwell assays) as well as cell imaging methods.

Scientific concepts and techniques that students will learn in this laboratory:

DP-iDP students will be trained in cell culture, including isolation, culture and characterisation of circulating endothelial progenitor cells. State of the art methods that the student will perform are immunohistochemical stainings, Western blot analysis, ELISA, real time qPCR and siRNA transfection. Moreover, students will gain insight in the analysis of methylation and gene expression data and pathway analysis. Besides these practical skills, students will be taught in knowledge on programming, placental development, and mechanisms how metabolic derangements affect cellular function.