Dataset Information

Transgenerational Obesity and Alteration of ARHGEF11 in the Rat Liver Induced by Intrauterine Hyperglycemia.

ABSTRACT: It is understood that intrauterine hyperglycemia increases the risk of obesity and diabetes in offspring of consecutive generations but its mechanisms remain obscure. This study is aimed at establishing an intrauterine hyperglycemia rat model to investigate the growth and glycolipid metabolic characteristics in transgenerational offspring and discuss the effects of Rho guanine nucleotide exchange factor 11 (ARHGEF11) and the PI3K/AKT signaling pathway in offspring development. The severe intrauterine hyperglycemia rat model was caused by STZ injection before mating, while offspring development and glycolipid metabolism were observed for the following two generations. The expression of ARHGEF11, ROCK1, PI3K, and AKT was tested in the liver and muscle tissue of F2 offspring. The results showed severe growth restriction in F1 offspring and obesity, fatty liver, and insulin resistance in female F2 offspring, especially the offspring of female intrauterine hyperglycemia-exposed parents (F2G?C?) and both (F2G?G?). The expression of ARHGEF11 and ROCK1 was significantly elevated; PI3K and phosphorylation of AKT were significantly decreased in liver tissues of F2G?C? and F2G?G?. Our study revealed that intrauterine hyperglycemia could cause obesity and abnormal glycolipid metabolism in female transgenerational offspring; the programming effect of the intrauterine environment could cause a more obvious phenotype in the maternal line. Further exploration suggested that increased expression of ARHGEF11 and ROCK1 and the decreased expression of PI3K and phosphorylation of AKT in the liver could be responsible for the abnormal development in F2 offspring.

SUBMITTER: Zhang W

PROVIDER: S-EPMC6757444 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Transgenerational Obesity and Alteration of ARHGEF11 in the Rat Liver Induced by Intrauterine Hyperglycemia.

Zhang Wanyi W Su Rina R Feng Hui H Lin Li L Wang Chen C Yang Huixia H

Journal of diabetes research 20190912

It is understood that intrauterine hyperglycemia increases the risk of obesity and diabetes in offspring of consecutive generations but its mechanisms remain obscure. This study is aimed at establishing an intrauterine hyperglycemia rat model to investigate the growth and glycolipid metabolic characteristics in transgenerational offspring and discuss the effects of Rho guanine nucleotide exchange factor 11 (ARHGEF11) and the PI3K/AKT signaling pathway in offspring development. The severe intraut ...[more]

PMID: 31612150

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Project description:Gestational diabetes mellitus (GDM) with intrauterine hyperglycemia induces a series of changes in the placenta, which have adverse effects on both the mother and fetus. Although some studies have examined these changes in the placenta, the differences resulting from fetal sex remain unelucidated. In this study, we established an intrauterine hyperglycemic model using ICR mice. We collected placental specimens before birth for histological observation using Hematoxylin and Eosin (HE) staining, along with Tandem Mass Tag (TMT) labeled proteomic analysis which was stratified by sex. In both male and female fetuses of the GDM group, body weight and placental weight were significantly lower compared to the control group. Additionally, the placenta-to-body weight ratio was higher, suggesting potential placental insufficiency. Histological analysis revealed smaller sizes and reduced thickness of the junctional zone and labyrinth in diabetic placentas at E18.5, along with ectopic accumulation of spongiotrophoblasts in the labyrinth. When the analysis was not segregated by sex, the GDM group showed 208 upregulated and 225 downregulated proteins in the placenta, primarily within the extracellular matrix and mitochondria. Altered biological processes included cholesterol metabolism and oxidative stress responses. After stratifying by sex, the male subgroup displayed 209 upregulated and 111 downregulated proteins, while the female subgroup exhibited 97 upregulated and 75 downregulated proteins. Among these, 64 differentially expressed proteins showed consistent trends across both sexes, primarily enriched in the JAK-STAT signaling pathway, complement and coagulation cascades, and metabolism-related modifications. The male subgroup showed a heightened tendency for immune-related pathway alterations, whereas the female subgroup manifested changes in branched-chain amino acid metabolism. The intrauterine hyperglycemic environment affects both placental morphology and proteomics, leading to shifts in energy metabolism, oxidative stress responses, and immune processes. Our study suggests that the observed differences in placental protein expression specific to each sex may provide an explanation for the varying impacts of GDM on offspring.

Dataset Information

Transgenerational Obesity and Alteration of ARHGEF11 in the Rat Liver Induced by Intrauterine Hyperglycemia.

Publications

Transgenerational Obesity and Alteration of ARHGEF11 in the Rat Liver Induced by Intrauterine Hyperglycemia.

Similar Datasets

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