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Reprod Toxicol. 2016 Jul;62:62-70. doi: 10.1016/j.reprotox.2016.04.015. Epub 2016 Apr 22.

Receptor for advanced glycation end products (RAGE) knockout reduces fetal dysmorphogenesis in murine diabetic pregnancy.

Author information

1
Department of Medical Cell Biology, Medical Faculty of Uppsala University, Biomedical Centre, P.O. Box 751, SE-75123 Uppsala, Sweden. Electronic address: andreas.ejdesjo@mcb.uu.se.
2
Department of Medicine I and Clinical Chemistry, University Hospital of Heidelberg, INF 410, Heidelberg and German Center for Diabetes Research (DZD), Heidelberg, Germany.
3
Department of Medical Cell Biology, Medical Faculty of Uppsala University, Biomedical Centre, P.O. Box 751, SE-75123 Uppsala, Sweden.

Abstract

The receptor for Advanced Glycation End products (RAGE) is implicated in the pathogenesis of diabetic complications, but its importance in diabetic embryopathy is unclear. We therefore investigated the role of RAGE in diabetic embryopathy using streptozotocin induced diabetes in female wild type (WT) C57Bl/6N and RAGE knockout C57Bl/6N (RAGE(-/-)) mice, mated with control males of the same genotype. Maternal diabetes induced more fetal resorption and malformation (facial skeleton, neural tube) in the WT than in the RAGE(-/-) fetuses. Maternal plasma glucose and methylgyoxal concentrations, as well as embryonic N(ε)-carboxymethyl-lysine (CML) levels were increased to the same extent in diabetic WT and RAGE(-/-) pregnancy. However, maternal diabetes induced increased fetal hepatic isoprostane 8-iso-PGF2α levels (oxidative stress marker) and embryonic activation of NFκB in WT only (not in RAGE(-/-) embryos). The association between RAGE knockout and diminished embryonic dysmorphogenesis in diabetic pregnancy suggests that embryonic RAGE activation is involved in diabetic embryopathy.

KEYWORDS:

AGE; Diabetes; Diabetic embryopathy; Experimental teratology; Neural tube defects; Oxidative stress; RAGE

PMID:
27109771
DOI:
10.1016/j.reprotox.2016.04.015
[Indexed for MEDLINE]

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