engleski

Global histone acetylation in diabetic embryopathy

Maternal diabetes increases the rate of congenital malformations in embryos, causing diabetic embryopathy which mostly affects heart and neural tube (embryonic precursor of central nervous system) in both humans and animal models. High maternal blood glucose concentration, which is presumably the major teratogenic factor, obstructs the process of embryonic neurulation (neural tube closure) by an unknown mechanism. Resulting open NTDs (neural tube defects) arise along rostrocaudal axis of the tube, affecting brain (exencephaly), spine (spina bifida aperta) or the entire neural tube (craniorachischisis). It has been shown that embryos developing in hyperglycemic milieu display disrupted gene expression pattern which seems rather non- specific, varying markedly between different mouse strains, or even between individual organisms of the same inbred strain. In an attempt to approach this issue from the point of genome-wide gene regulation, we analyzed global histone H3 and histone H4 acetylaton in 44 non-obese diabetic (NOD) mouse embryo specimens at midgestation (embryonic day 10.5). Hypoacetilation of both H3 and H4 has been detected in embryos with spina bifida aperta and craniorachischisis, but not exencephaly. Further, more detailed analysis of histone acetylation at gene promoters is needed to establish potential relationship between histone acetylation and transcriptional regulation in diabetic embryopathy.

diabetic embryopathy; neural tube defects; histone acetylation

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