Mary Loeken

..To review the current understanding of the molecular causes of birth defects resulting from diabetic pregnancy, with a focus on neural tube defects...

..Evidence in support of this model, in which excess glucose metabolism inhibits expression of Pax3, thereby derepressing p53-dependent apoptosis of neuroepithelium and leading to NTD will be discussed...

..These observations suggest that maternal hyperglycemia depletes O(2) in the embryo and that this contributes to oxidative stress and the adverse effects of maternal hyperglycemia on embryo development...

..Here we tested whether maternal diabetes, through hyperglycemia-induced oxidative stress, before the onset of CNC delamination, impairs CNC migration and cardiac outflow tract septation...

..To evaluate whether there were differences in acquisition of research grant support between male and female faculty at eight Harvard Medical School-affiliated institutions...

..This, then provides a cellular explanation for the cardiac outflow tract and neural tube and defects induced by diabetic pregnancy...

..Moreover, if susceptibility to diabetic embryopathy is variable in humans as well as in mice, it may be possible to screen individuals at increased risk for this complication of diabetes...

..These results suggest that Pax-3 regulates neural tube closure by inhibiting p53-dependent apoptosis, rather than by inducing neural tube-specific gene expression...

..CONCLUSIONS: Activation of the hexosamine pathway causes oxidative stress through depletion of GSH and consequent disruption of embryo gene expression. Activation of this pathway may contribute to diabetic teratogenesis...

..The focus of this review will be on the role of oxidative stress in the etiology of diabetic complications...

..These data indicate that hyperglycemia just before organogenesis activates the DAG-PKC cascade and is correlated with congenital defects...

..These results suggest that culture of cells derived from murine blastocysts in physiological oxygen and glucose reduces oxidant stress, which increases the success of establishing new embryonic stem cell lines...

..These results indicate that Pax3 is required for cardiac outflow tract septation because it blocks p53-dependent processes during CNC migration...

..This positive interaction between RA and maternal diabetes may have implications for humans in suggesting increased susceptibility to environmental teratogens during diabetic pregnancy...

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..This research will significantly advance our knowledge of how closure and dorsalization of the neural tube is regulated, and provide new information on the molecular mechanisms by which diabetic pregnancy causes NTD. ..

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..This project will investigate how altered expression of a gene that is required during early embryo development, resulting from diabetic pregnancy, leads to birth defects. ..

..These experiments will reveal, in a way that has not been done in the past, the molecular mechanisms by which embryonic development is during diabetic pregnancy. ..

..Aim 3 will test whether overexpression of factors that regulate both developmental control and stress-responsive genes protects embryos from the altered gene expression, apoptosis, and NTD associated with excess glucose. ..

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