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National Institute of Environmental Health Sciences

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Publication Detail

Title: Targeted Multiplex Gene Expression Profiling to Measure High-Fat Diet and Metformin Effects on Fetal Gene Expression in a Mouse Model.

Authors: Vora, Neeta L; Grace, Matthew R; Smeester, Lisa; Dotters-Katz, Sarah K; Fry, Rebecca C; Bae-Jump, Victoria; Boggess, Kim

Published In Reprod Sci, (2019 05)

Abstract: Maternal obesity and excessive gestational weight gain (GWG) are associated with delivery of a large-for-gestational-age infant. We used a high-fat diet (HFD) mouse model to separate the effect of maternal obesity from excessive GWG on fetal growth. Our objective was to identify fetal gene expression changes in an HFD and control diet (CD) mouse model with and without metformin exposure.Normal weight timed-pregnant (Female Friend virus B) strain mice were allocated on day e0.5 to receive HFD or CD and either plain water or metformin (2.5 mg/mL in drinking water). Dams were euthanized on day e17.5 and fetal livers harvested and frozen at -80°C. RNA was extracted and hybridized to a customized 96-gene Nanostring panel focused on angiogenesis, inflammation, and growth gene expression. Fetal liver gene expression was compared between metformin and plain water groups using analysis of variance. Significant differences in gene expression, defined by a false discovery controlled q value <0.01, were then analyzed using Ingenuity pathway analysis (IPA).In HFD-fed dams, compared to controls, the metformin-treated group had significantly lower fetal weight and 39 differentially expressed liver genes; 15 (38%) were in the growth/angiogenesis gene expression network. IPA predicted that fetal liver gene upregulation associated with metformin exposure is a result of metformin inhibition of the common upstream regulator, phosphatase and tensin homolog ( PTEN).Metformin-exposed fetuses from dams fed HFD and CD have significant gene expression differences in genes specific to growth and angiogenesis pathways in the fetal liver. Diet alone did not alter fetal liver gene expression.

PubMed ID: 29976116 Exiting the NIEHS site

MeSH Terms: No MeSH terms associated with this publication

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