Abstract | BACKGROUND: OBJECTIVE: STUDY DESIGN: A mouse model of maternal type 2 diabetes mellitus was established by feeding female mice a high-fat diet (60% fat). After 15 weeks on the high-fat diet, the mice showed characteristics of maternal type 2 diabetes mellitus. Control dams were either fed a normal diet (10% fat) or the high-fat diet during pregnancy only. Female mice from the high-fat diet group and the 2 control groups were mated with male mice that were fed a normal diet. At E12.5, embryonic hearts were harvested to determine the levels of lipid peroxides and superoxide, endoplasmic reticulum stress markers, cleaved caspase 3 and 8, and apoptosis. E17.5 embryonic hearts were harvested for the detection of congenital heart defect formation using India ink vessel patterning and histological examination. RESULTS: Maternal type 2 diabetes mellitus significantly induced ventricular septal defects and persistent truncus arteriosus in the developing heart, along with increasing oxidative stress markers, including superoxide and lipid peroxidation; endoplasmic reticulum stress markers, including protein levels of phosphorylated- protein kinase RNA-like endoplasmic reticulum kinase, phosphorylated-IRE1α, phosphorylated-eIF2α, C/EBP homologous protein, and binding immunoglobulin protein; endoplasmic reticulum chaperone gene expression; and XBP1 messenger RNA splicing, as well as increased cleaved caspase 3 and 8 in embryonic hearts. Furthermore, maternal type 2 diabetes mellitus triggered excessive apoptosis in ventricular myocardium, endocardial cushion, and outflow tract of the embryonic heart. CONCLUSION: Similar to those observations in type 1 diabetic embryopathy, maternal type 2 diabetes mellitus causes heart defects in the developing embryo manifested with oxidative stress, endoplasmic reticulum stress, and excessive apoptosis in heart cells.
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Authors | Yanqing Wu, E Albert Reece, Jianxiang Zhong, Daoyin Dong, Wei-Bin Shen, Christopher R Harman, Peixin Yang |
Journal | American journal of obstetrics and gynecology
(Am J Obstet Gynecol)
Vol. 215
Issue 3
Pg. 366.e1-366.e10
(09 2016)
ISSN: 1097-6868 [Electronic] United States |
PMID | 27038779
(Publication Type: Journal Article)
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Copyright | Copyright © 2016 Elsevier Inc. All rights reserved. |
Chemical References |
- Endoplasmic Reticulum Chaperone BiP
- Heat-Shock Proteins
- X-Box Binding Protein 1
- Xbp1 protein, mouse
- Transcription Factor CHOP
- Protein Kinases
- Ern1 protein, mouse
- Protein Serine-Threonine Kinases
- eIF2alpha kinase, mouse
- Endoribonucleases
- Casp8 protein, mouse
- Caspase 3
- Caspase 8
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Topics |
- Animals
- Apoptosis
- Caspase 3
(metabolism)
- Caspase 8
(metabolism)
- Diabetes Mellitus, Experimental
- Diabetes, Gestational
- Embryo, Mammalian
- Endoplasmic Reticulum
(metabolism)
- Endoplasmic Reticulum Chaperone BiP
- Endoplasmic Reticulum Stress
- Endoribonucleases
(metabolism)
- Female
- Heart Defects, Congenital
(embryology, pathology)
- Heat-Shock Proteins
(metabolism)
- Lipid Peroxidation
- Mice, Inbred C57BL
- Myocardium
(metabolism, pathology)
- Oxidative Stress
- Phosphorylation
- Pregnancy
- Protein Kinases
(metabolism)
- Protein Serine-Threonine Kinases
(metabolism)
- RNA Splicing
- Transcription Factor CHOP
(metabolism)
- X-Box Binding Protein 1
(genetics)
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