Prof. Dr. Eckhard Wolf

Developmental impact of maternal diabetes mellitus - a molecular systems study of oocytes, embryos and their maternal environment in genetically designed mouse and pig models

Molecular Animal Breeding and Biotechnology - Gene Center

Ludwigs-Maximilians-University Munich
Feodor-Lynen-Str. 25 
81377 Munich


Tel: +49 (0)89/21 80 76 800
Fax: +49 (0)89/21 80 76 849 



Deutsche Version


The global prevalence of diabetes mellitus is dramatically increasing. Maternal diabetes is known to adversely affect embryo development and pregnancy outcomes. These effects may be associated with structural, functional or molecular changes, at different levels, from compromised oocyte competence to alterations of the uterine environment. We will use corresponding mouse and pig models expressing mutant insulin molecules, leading to permanent hyperglycemia. Oocytes recovered from these models will be analyzed for structural, functional and molecular abnormalities (transcriptome, proteome, epigenome) as compared to control oocytes. In order to address the effect of maternal hyperglycemia on preimplantation embryonic development, embryos from wild-type donor animals will be transferred to synchronized diabetic and non-diabetic recipient animals.

Oocyte in Focus - Courtesy by Dr. Felix A. Habermann
Oocyte in Focus - Courtesy by Dr. Felix A. Habermann

The development of embryos to the blastocyst in the diabetic maternal environment will be monitored and embryos will be recovered and processed for structural (multi-color confocal laser scanning microscopy, transmission electron microscopy) and quantitative molecular analyses targeting RNAs, proteins and DNA modifications. In addition we will perform RNA and protein expression profiling of the uterine endometrium to evaluate effects of hyperglycemia on maternal recognition of pregnancy. These studies will for the first time provide systemic insights into developmental consequences of maternal hyperglycemia. Thereby, pig models will be used to answer questions on important issues of early human development that cannot be adequately simulated in mouse models.

Group members

PD Dr. Stefan Bauersachs

Dr. Simone Renner

Dr. Barbara Keßler

Dr. Georg J. Arnold

Dr. Helmut Blum

Dr. Felix A. Habermann

Publications within BioSysNet

Graf A, Krebs S, Zakhartchenko V, Schwalb B, Blum H, Wolf E (2014). Fine mapping of genome activation in bovine embryos by RNA sequencing. Proc Natl Acad Sci U S A 111(11):4139-44. 


Renner S, Braun-Reichhart C, Blutke A, Herbach N, Emrich D, Streckel E, Wünsch A, Kessler B, Kurome M, Bähr A, Klymiuk N, Krebs S, Puk O, Nagashima H, Graw J, Blum H, Wanke R, Wolf E (2013). Permanent neonatal diabetes in INS(C94Y) transgenic pigs. Diabetes 62(5):1505-11. 

Publications before BioSysNet

Aigner B, Rathkolb B, Herbach N, Hrabé de Angelis M, Wanke R, Wolf E. Diabetes models by screen for hyperglycemia in phenotype-driven ENU mouse mutagenesis projects. Am J Physiol Endocrinol Metab. 2008 Feb;294(2):E232-40. Epub 2007 Dec 4. PubMed PMID: 18056790.


Aigner B, Renner S, Kessler B, Klymiuk N, Kurome M, Wünsch A, Wolf E. Transgenic pigs as models for translational biomedical research. J Mol Med (Berl). 2010 Jul;88(7):653-64. Epub 2010 Mar 26. PubMed PMID: 20339830.


Bauersachs S, Ulbrich SE, Zakhartchenko V, Minten M, Reichenbach M, Reichenbach HD, Blum H, Spencer TE, Wolf E. The endometrium responds differently to cloned versus fertilized embryos. Proc Natl Acad Sci U S A. 2009 Apr 7;106(14):5681-6. Epub 2009 Mar 23. PubMed PMID: 19307558.


Bauersachs S, Wolf E. Molecular networks as sensors and drivers of uterine receptivity in livestock. In: MFW te Pas, H Woelders, A Bannink (eds) Systems Biology in Livestock Sciences, John Wiley & Sons, Ltd. 2011, pp 161-190.

Berendt FJ, Fröhlich T, Bolbrinker P, Boelhauve M, Güngör T, Habermann FA, Wolf E, Arnold GJ. Highly sensitive saturation labeling reveals changes in abundance of cell cycle-associated proteins and redox enzyme variants during oocyte maturation in vitro. Proteomics. 2009 Feb;9(3):550-64. PubMed PMID: 19137544.


Dahlhoff M, Grzech M, Habermann FA, Wolf E, Schneider MR. A transgenic mouse line expressing cre recombinase in pancreatic β-cells. Genesis. 2011 Oct 13. doi:10.1002/dvg.20817. [Epub ahead of print] PubMed PMID: 21998080.


Grzech M, Dahlhoff M, Herbach N, Habermann FA, Renner-Müller I, Wanke R, Flaswinkel H, Wolf E, Schneider MR. Specific transgene expression in mouse pancreatic beta-cells under the control of the porcine insulin promoter. Mol Cell Endocrinol. 2010 Feb 5;315(1-2):219-24. Epub 2009 Aug 12. PubMed PMID: 19682540.


Herbach N, Bergmayr M, Göke B, Wolf E, Wanke R. Postnatal development of numbers and mean sizes of pancreatic islets and beta-cells in healthy mice and GIPR(dn) transgenic diabetic mice. PLoS One. 2011;6(7):e22814. Epub 2011 Jul 26. PubMed PMID: 21818396.


Herbach N, Goeke B, Schneider M, Hermanns W, Wolf E, Wanke R. Overexpression of a dominant negative GIP receptor in transgenic mice results in disturbed postnatal pancreatic islet and beta-cell development. Regul Pept. 2005 Feb 15;125(1-3):103-17. PubMed PMID: 15582721.


Herbach N, Göke B, Wolf E, Wanke R. Diets influence the diabetic phenotype of transgenic mice expressing a dominant negative glucose-dependent insulinotropic polypeptide receptor (GIPRdn). Regul Pept. 2008 Feb 7;146(1-3):260-70. Epub 2007 Oct 23. PubMed PMID: 18031839.


Herbach N, Rathkolb B, Kemter E, Pichl L, Klaften M, de Angelis MH, Halban PA, Wolf E, Aigner B, Wanke R. Dominant-negative effects of a novel mutated Ins2 allele causes early-onset diabetes and severe beta-cell loss in Munich Ins2C95S mutant mice. Diabetes. 2007 May;56(5):1268-76. Epub 2007 Feb 15. PubMed PMID: 17303807.


Herbach N, Schairer I, Blutke A, Kautz S, Siebert A, Göke B, Wolf E, Wanke R. Diabetic kidney lesions of GIPRdn transgenic mice: podocyte hypertrophy and thickening of the GBM precede glomerular hypertrophy and glomerulosclerosis. Am J Physiol Renal Physiol. 2009 Apr;296(4):F819-29. Epub 2009 Feb 11. PubMed PMID: 19211686.


Kautz S, van Bürck L, Schuster M, Wolf E, Wanke R, Herbach N. Early insulin therapy prevents beta cell loss in a mouse model for permanent neonatal diabetes (Munich Ins2(C95S)). Diabetologia. 2012 Feb;55(2):382-91. Epub 2011 Nov 18. PubMed PMID: 22095234.


Klymiuk N, Böcker W, Schönitzer V, Bähr A, Radic T, Fröhlich T, Wünsch A, Keßler B, Kurome M, Schilling E, Herbach N, Wanke R, Nagashima H, Mutschler W, Arnold GJ, Schwinzer R, Schieker M, Wolf E. First inducible transgene expression in porcine large animal models. FASEB J. 2012 Mar;26(3):1086-99. Epub 2011 Dec 1. PubMed PMID: 22138035.


Klymiuk N, van Buerck L, Bähr A, Offers M, Kessler B, Wuensch A, Kurome M, Thormann M, Lochner K, Nagashima H, Herbach N, Wanke R, Seissler J, Wolf E. Xenografted islet cell clusters from INSLEA29Y transgenic pigs rescue diabetes and prevent immune rejection in humanized mice. Diabetes. 2012 Apr 20. [Epub ahead of print]. PubMed PMID: 22522620.


Leidenfrost S, Boelhauve M, Reichenbach M, Güngör T, Reichenbach HD, Sinowatz F, Wolf E, Habermann FA. Cell arrest and cell death in mammalian preimplantation development: lessons from the bovine model. PLoS One. 2011;6(7):e22121. Epub 2011 Jul 21. PubMed PMID: 21811561.


Østrup E, Bauersachs S, Blum H, Wolf E, Hyttel P. Differential endometrial gene expression in pregnant and nonpregnant sows. Biol Reprod. 2010 Aug 1;83(2):277-85. Epub 2010 Apr 14. PubMed PMID: 20393170.


Paula-Lopes FF, Boelhauve M, Habermann FA, Sinowatz F, Wolf E. Leptin promotes meiotic progression and developmental capacity of bovine oocytes via cumulus cell-independent and dependent mechanisms. Biol Reprod. 2007 Mar;76(3):532-41. Epub 2006 Nov 8. PubMed PMID: 17093200.


Renner S, Fehlings C, Herbach N, Hofmann A, von Waldthausen DC, Kessler B, Ulrichs K, Chodnevskaja I, Moskalenko V, Amselgruber W, Göke B, Pfeifer A, Wanke R, Wolf E. Glucose intolerance and reduced proliferation of pancreatic beta-cells in transgenic pigs with impaired glucose-dependent insulinotropic polypeptide function. Diabetes. 2010 May;59(5):1228-38. Epub 2010 Feb 25. PubMed PMID: 20185813.


Renner S, Römisch-Margl W, Prehn C, Krebs S, Adamski J, Göke B, Blum H, Suhre K, Roscher AA, Wolf E. Changing metabolic signatures of amino acids and lipids during the prediabetic period in a pig model with impaired incretin function and reduced β-cell mass. Diabetes. 2012 Apr 9. [Epub ahead of print] PubMed PMID:22492530.


van Bürck L, Blutke A, Kautz S, Rathkolb B, Klaften M, Wagner S, Kemter E, Hrabé de Angelis M, Wolf E, Aigner B, Wanke R, Herbach N. Phenotypic and pathomorphological characteristics of a novel mutant mouse model for maturity-onset diabetes of the young type 2 (MODY 2). Am J Physiol Endocrinol Metab. 2010 Mar;298(3):E512-23. Epub 2009 Dec 1. PubMed PMID: 19952346.