| Autor: |
Gutierrez, J. Claudio, Prater, M. Renee, Smith, Bonnie J., Freeman, Larry E., Mallela, Murali K., Holladay, Steven D. |
| Zdroj: |
Birth Defects Research Part B: Developmental and Reproductive Toxicology; October 2009, Vol. 86 Issue: 5 p409-415, 7p |
| Abstrakt: |
BACKGROUND: 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. Prebreeding maternal immune stimulation, using Freunds 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. METHODS: Female CD1 mice were injected with 200 mgkg of streptozocin STZ to induce insulindependent 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 RTPCR. RESULTS: Early apoptotic cells and late apoptoticnecrotic cells were significantly increased in fetal hearts from STZ or STZFCA dams. Pretreatment with FCA reduced late apoptoticnecrotic 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 proapoptotic genes Casp3 and Casp9 was decreased by diabetes, while the antiapoptotic gene Bcl2 was increased. CONCLUSIONS: Maternal hyperglycemia causes dysregulated apoptosis of fetal myocardial cells. Such effect may be prevented by maternal immune stimulation. Birth Defects Res Part B86:409–415, 2009. © 2009 WileyLiss, Inc. |
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