Late-gestation ventricular myocardial reduction in fetuses of hyperglycemic CD1 mice is associated with increased apoptosis
| Autor: | Steven D. Holladay, Larry E. Freeman, J. Claudio Gutierrez, Murali K. Mallela, M. Renee Prater, Bonnie J. Smith |
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| Rok vydání: | 2009 |
| Předmět: |
Blood Glucose
Heart Defects Congenital Male Embryology medicine.medical_specialty Programmed cell death Heart Ventricles Health Toxicology and Mutagenesis Freund's Adjuvant Pregnancy in Diabetics Apoptosis Gestational Age Mice Inbred Strains Toxicology Article Diabetes Mellitus Experimental Flow cytometry Mice Pregnancy Diabetes mellitus Internal medicine Animals Medicine Myocyte Myocytes Cardiac Maternal-Fetal Exchange Fetus medicine.diagnostic_test business.industry Gene Expression Profiling Myocardium Flow Cytometry medicine.disease Diabetes Mellitus Type 1 Endocrinology Freund's adjuvant Hyperglycemia Gestation Female business Developmental Biology |
| Zdroj: | Birth Defects Research Part B: Developmental and Reproductive Toxicology. 86:409-415 |
| ISSN: | 1542-9741 1542-9733 |
| DOI: | 10.1002/bdrb.20212 |
| Popis: | Previous work in our laboratory showed reduced myocardium and dilated ventricular chambers in gestation day (GD) 17 hearts that were collected from hyperglycemic CD1 mouse dams. Pre-breeding maternal immune stimulation, using Freund's complete adjuvant (FCA), diminished the severity of these fetal heart lesions. The following experiments were performed to detect possible changes in fetal heart apoptotic cell death, under hyperglycemic conditions and with or without maternal immune stimulation.Female CD1 mice were injected with 200 mg/kg of streptozocin (STZ) to induce insulin-dependent diabetes mellitus. Half of these mice received prior FCA injection. Fetal hearts were collected on GD 17 and myocardial apoptotic cells were quantified using flow cytometry. A panel of apoptosis regulatory genes (Bcl2, p53, Casp3, Casp9, PkCe) was then examined in the fetal myocardium using RT-PCR.Early apoptotic cells and late apoptotic/necrotic cells were significantly increased in fetal hearts from STZ or STZ+FCA dams. Pre-treatment with FCA reduced late apoptotic/necrotic cells to control level, suggesting some cell death protection was rendered by FCA. Paradoxically in the face of such increased cell death, the expression of pro-apoptotic genes Casp3 and Casp9 was decreased by diabetes, while the anti-apoptotic gene Bcl2 was increased.Maternal hyperglycemia causes dys-regulated apoptosis of fetal myocardial cells. Such effect may be prevented by maternal immune stimulation. |
| Databáze: | OpenAIRE |
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