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Background Diabetes mellitus in pregnancy causes defects in infant heart, includingthe outflow tracts (OFTs). Development of the aorta and pulmonary artery, which are derived from the common OFT in the embryo, is regulated by the transforming growth factor β (TGFβ) and Wnt families, and can be perturbed by hyperglycemia-generated intracellular stress conditions. However, the underlying cellular and molecular mechanisms remain to be delineated. Methods Female mice were induced diabetic with streptozotocin. Embryonic and fetal OFTs were examined morphologically and histologically. Cell proliferation was assessed using BrdU-incorporation assay. Oxidative and endoplasmic reticulum (ER) stresses and TGFβ factors were detected using immunohistochemistry. The expression of genes in the Wnt signaling system was assessed using real-time RT-PCR array. The role of Activin-A in cell proliferation was addressed by treating embryos cultured in high glucose with Activin-A. Results Maternal diabetes caused complex abnormalities in the OFT, including aortic and pulmonary stenosis and persistent truncus arteriosus. The development of the endocardial cushions was suppressed, manifested with insufficient cellularization of the tissues. Cell proliferation was significantly decreased under oxidative and ER stress conditions. The expression of genes in the Wnt signaling was significantly altered. Activin-A and Smad3 were found to be expressed in the OFT. Treatment with Activin-A rescued cell proliferation in the endocardial cushions. Conclusions Maternal diabetes generates oxidative and ER stress conditions, suppresses TGFβ and Wnt signaling, inhibits cell proliferation and cellularization of the endocardial cushions, leading to OFT septal defects. Activin-A plays a role in hyperglycemia-suppressed proliferation of the endocardial cells.
Background Diabetes mellitus in pregnancy causes defects in infant heart, includingthe outflow tracts (OFTs). Development of the aorta and pulmonary artery, which are derived from the common OFT in the embryo, is regulated by the transforming growth factor β (TGFβ) and Wnt families, and can be perturbed by hyperglycemia-generated intracellular stress conditions. However, the underlying cellular and molecular mechanisms remain to be delineated. Methods Female mice were induced diabetic with streptozotocin. Embryonic and fetal OFTs were examined morphologically and histologically. Cell proliferation was assessed using BrdU-incorporation assay. Oxidative and endoplasmic reticulum (ER) stresses and TGFβ factors were detected using immunohistochemistry. The expression of genes in the Wnt signaling system was assessed using real-time RT-PCR array. The role of Activin-A in cell proliferation was addressed by treating embryos cultured in high glucose with Activin-A. Results Maternal diabetes caused complex abnormalities in the OFT, including aortic and pulmonary stenosis and persistent truncus arteriosus. The development of the endocardial cushions was suppressed, manifested with insufficient cellularization of the tissues. Cell proliferation was significantly decreased under oxidative and ER stress conditions. The expression of genes in the Wnt signaling was significantly altered. Activin-A and Smad3 were found to be expressed in the OFT. Treatment with Activin-A rescued cell proliferation in the endocardial cushions. Conclusions Maternal diabetes generates oxidative and ER stress conditions, suppresses TGFβ and Wnt signaling, inhibits cell proliferation and cellularization of the endocardial cushions, leading to OFT septal defects. Activin-A plays a role in hyperglycemia-suppressed proliferation of the endocardial cells.
The Yangtze River has been a source of life and prosperity for the Chinese people for centuries and is a habitat for a remarkable variety of aquatic species. But the river suffers from huge amounts of urban sewage, agricultural effluents, and industrial wastewater as well as ship navigation wastes along its course. With respect to the vast amounts of water and sediments discharged by the Yangtze River, it is reasonable to ask whether the pollution problem may be solved by simple dilution. This article reviews the past two decades of published research on organic pollutants in the Yangtze River and several adjacent water bodies connected to the main stream, according to a holistic approach. Organic pollutant levels and potential effects of water and sediments on wildlife and humans, measured in vitro, in vivo, and in situ, were critically reviewed. The contamination with organic pollutants, including polycyclic aromatic hydrocarbons, polychlorinated biphenyls (PCBs), organochlorine pesticides (OCPs), polychlorinated dibenzo-p-dioxins/polychlorinated dibenzofurans, polybrominated diphenyl ethers (PBDEs), perfluorinated compounds (PFCs), and others, of water and sediment along the river was described. Especially Wuhan section and the Yangtze Estuary exhibited stronger pollution than other sections. Bioassays, displaying predominantly the endpoints mutagenicity and endocrine disruption, applied at sediments, drinking water, and surface water indicated a potential health risk in several areas. Aquatic organisms exhibited detectable concentrations of toxic compounds like PCBs, OCPs, PBDEs, and PFCs. Genotoxic effects could also be assessed in situ in fish. To summarize, it can be stated that dilution reduces the ecotoxicological risk in the Yangtze River, but does not eliminate it. Keeping in mind an approximately 14 times greater water discharge compared to the major European river Rhine, the absolute pollution mass transfer of the Yangtze River is of severe concern for the environmental quality of its estuary and the East China Sea. Based on the review, further research needs have been identified.
Background Complete atrioventricular canal defects (CAVC) are a common heart defect, but few epidemiologic studies have evaluated nonsyndromic CAVC. Risk factors for nonsyndromic CAVC have not been well established. Methods To assess the relationship between risk for nonsyndromic CAVC in offspring and several sociodemographic and reproductive parental factors, including maternal diabetes and obesity, we conducted Poisson regression analyses, using data ascertained through the Texas Birth Defects Registry, a large, population-based birth defects registry. Data were evaluated for 563 nonsyndromic cases with CAVC. Results Significant associations were observed between nonsyndromic CAVC in offspring and maternal pregestational diabetes (adjusted prevalence ratio (aPR): 6.74, 95% confidence interval (CI): 3.67–12.37), gestational diabetes [aPR: 1.69, 95% CI: 1.03, 2.79], and obesity [aPR: 1.69, 95% CI: 1.24, 2.30]. Comments Our findings add nonsyndromic CAVC to the growing list of birth defects that appear to be associated with maternal diabetes and obesity.
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