| Maternal diabetes impairs gastrulation and insulin and IGF-I receptor expression in rabbit blastocysts. | |
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MedLine Citation:
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PMID: 20631000 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Women with type 1 diabetes are subfertile. Diabetes negatively affects pregnancy by causing early miscarriage and poor prenatal outcomes. In this study we examine consequences of maternal type 1 diabetes on early embryo development, metabolic gene expression, and the pattern of insulin receptor (IR) and IGF-I receptor (IGF-IR) distribution in rabbit blastocysts. In female rabbits, type 1 diabetes was induced by alloxan treatment. Six-day-old blastocysts were recovered and assessed for receptor distribution and metabolic gene expression. In vitro culture of blastocysts was performed in medium containing 1 mm, 10 mm, or 25 mm glucose, simulating normo- and hyperglycemic developmental condition in vitro. The fertility rate of the diabetic rabbits clearly mirrored subfertility with a drop in blastocyst numbers by 40% (13.3 blastocysts in diabetic vs. 21.9 in control females). In blastocysts onset and progression of gastrulation was delayed and expression of IR and IGF-IR and their metabolic target genes (hexokinase, phosphoenolpyruvate carboxykinase), both in vivo and in vitro, was down-regulated. The amount of apoptotic cells in the embryonic disc was increased, correlating closely with the reduced transcription of the bcl-x(L) gene. Blastocyst development is clearly impaired by type 1 diabetes during early pregnancy. Insulin-stimulated metabolic genes and IR and IGF-IR are down-regulated, resulting in reduced insulin and IGF sensitivity and a delay in development. Dysregulation of the IGF system and embryonic glucose metabolism are potential reasons for diabetogenous subfertility and embryopathies and start as soon as during the first days of life. |
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Authors:
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Nicole Ramin; René Thieme; Sünje Fischer; Maria Schindler; Thomas Schmidt; Bernd Fischer; Anne Navarrete Santos |
Publication Detail:
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Type: Journal Article Date: 2010-07-14 |
Journal Detail:
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Title: Endocrinology Volume: 151 ISSN: 1945-7170 ISO Abbreviation: Endocrinology Publication Date: 2010 Sep |
Date Detail:
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Created Date: 2010-08-25 Completed Date: 2010-10-04 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0375040 Medline TA: Endocrinology Country: United States |
Other Details:
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Languages: eng Pagination: 4158-67 Citation Subset: AIM; IM |
Affiliation:
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Department of Anatomy and Cell Biology, Martin Luther University Faculty of Medicine, Grosse Steinstrasse 52, D-06097 Halle (Saale), Germany. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Alloxan Animals Apoptosis / physiology Blastocyst / cytology, metabolism* Blood Glucose / metabolism Diabetes Mellitus, Experimental / blood, chemically induced, physiopathology Diabetes Mellitus, Type 1 / blood, chemically induced, physiopathology* Embryo Culture Techniques Embryo, Mammalian / cytology, embryology, metabolism Enzyme-Linked Immunosorbent Assay Female Gastrulation / genetics, physiology Gene Expression Regulation, Developmental Immunoblotting In Situ Nick-End Labeling Insulin / blood, genetics*, metabolism Phosphoenolpyruvate Carboxykinase (ATP) / genetics, metabolism Pregnancy Pregnancy in Diabetics / blood, physiopathology Rabbits Receptor, IGF Type 1 / genetics*, metabolism Receptor, Insulin / genetics, metabolism Reverse Transcriptase Polymerase Chain Reaction |
| Chemical | |
Reg. No./Substance:
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0/Blood Glucose; 11061-68-0/Insulin; 50-71-5/Alloxan; EC 2.7.10.1/Receptor, IGF Type 1; EC 2.7.10.1/Receptor, Insulin; EC 4.1.1.49/Phosphoenolpyruvate Carboxykinase (ATP) |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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