Dataset Information

Maternal High Fat Diet-Induced Obesity Modifies Histone Binding and Expression of Oxtr in Offspring Hippocampus in a Sex-Specific Manner.

ABSTRACT: Maternal obesity during pregnancy increases risk for neurodevelopmental disorders in offspring, although the underlying mechanisms remain unclear. Epigenetic deregulation associates with many neurodevelopmental disorders, and recent evidence indicates that maternal nutritional status can alter chromatin marks in the offspring brain. Thus, maternal obesity may disrupt epigenetic regulation of gene expression during offspring neurodevelopment. Using a C57BL/6 mouse model, we investigated whether maternal high fat diet (mHFD)-induced obesity alters the expression of genes previously implicated in the etiology of neurodevelopmental disorders within the Gestational Day 17.5 (GD 17.5) offspring hippocampus. We found significant two-fold upregulation of oxytocin receptor (Oxtr) mRNA in the hippocampus of male, but not female, GD 17.5 offspring from mHFD-induced obese dams (p < 0.05). To determine whether altered histone binding at the Oxtr gene promoter may underpin these transcriptional changes, we then performed chromatin immunoprecipitation (ChIP). Consistent with the Oxtr transcriptional changes, we observed increased binding of active histone mark H3K9Ac at the Oxtr transcriptional start site (TSS) in the hippocampus of mHFD male (p < 0.05), but not female, offspring. Together, these data indicate an increased vulnerability of male offspring to maternal obesity-induced changes in chromatin remodeling processes that regulate gene expression in the developing hippocampus, and contributes to our understanding of how early life nutrition affects the offspring brain epigenome.

SUBMITTER: Glendining KA

PROVIDER: S-EPMC6359595 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Maternal High Fat Diet-Induced Obesity Modifies Histone Binding and Expression of <i>Oxtr</i> in Offspring Hippocampus in a Sex-Specific Manner.

Glendining Kelly A KA Jasoni Christine L CL

International journal of molecular sciences 20190115 2

Maternal obesity during pregnancy increases risk for neurodevelopmental disorders in offspring, although the underlying mechanisms remain unclear. Epigenetic deregulation associates with many neurodevelopmental disorders, and recent evidence indicates that maternal nutritional status can alter chromatin marks in the offspring brain. Thus, maternal obesity may disrupt epigenetic regulation of gene expression during offspring neurodevelopment. Using a C57BL/6 mouse model, we investigated whether m ...[more]

PMID: 30650536

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Project description:Maternal diabetes-induced fetal programming predisposes offspring to type 2 diabetes, cardiovascular disease, and obesity in adulthood. However, lifelong health and disease trajectories depend on several factors and nutrition is one of the main ones. We intend to understand the role of maternal diabetes-induced fetal programming and its association with a high-fat diet during lifelong in the female F1 generation focusing on reproductive outcomes and the possible changes in physiological systems during pregnancy as well as the repercussions on the F2 generation at birth. For this, we composed four groups: F1 female pups from control (OC) or from diabetic dams (OD) and fed with standard (SD) or high-fat diet from weaning to full-term pregnancy. During pregnancy, glucose intolerance and insulin sensitivity were evaluated. In a full-term pregnancy, the maternal blood and liver were collected to evaluate redox status markers. The maternal blood, placental tissue, and fetal blood (pool) were collected to evaluate adiponectin and leptin levels. Maternal reproductive parameters were evaluated as well. Maternal diabetes and high-fat diet consumption, in isolation, were both responsible for increased infertility rates and fasting glucose levels in the F1 generation and fetal growth restriction in the F2 generation. The association of both conditions showed, in addition to those, increased lipoperoxidation in maternal erythrocytes, regardless of the increased endogenous antioxidant enzyme activities, glucose intolerance, decreased number of implantation sites and live fetuses, decreased litter, fetal and placental weight, increased preimplantation losses, and increased fetal leptin serum levels. Thus, our findings show that fetal programming caused by maternal diabetes or lifelong high-fat diet consumption leads to similar repercussions in pregnant rats. In addition, the association of both conditions was responsible for glucose intolerance and oxidative stress in the first generation and increased fetal leptin levels in the second generation. Thus, our findings show both the F1 and F2 generations harmed health after maternal hyperglycemic intrauterine environment and exposure to a high-fat diet from weaning until the end of pregnancy.

Dataset Information

Maternal High Fat Diet-Induced Obesity Modifies Histone Binding and Expression of Oxtr in Offspring Hippocampus in a Sex-Specific Manner.

Publications

Maternal High Fat Diet-Induced Obesity Modifies Histone Binding and Expression of <i>Oxtr</i> in Offspring Hippocampus in a Sex-Specific Manner.

Similar Datasets

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