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18 January 2018 Diet-induced obesity alters the maternal metabolome and early placenta transcriptome and decreases placenta vascularity in the mouse
Tami J. Stuart, Kathleen O'Neill, David Condon, Issac Sasson, Payel Sen, Yunwei Xia, Rebecca A. Simmons
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Abstract

Maternal obesity is associated with an increased risk of obesity and metabolic disease in offspring. Increasing evidence suggests that the placenta plays an active role in fetal programming. In this study, we used a mouse model of diet-induced obesity to demonstrate that the abnormal metabolic milieu of maternal obesity sets the stage very early in pregnancy by altering the transcriptome of placenta progenitor cells in the preimplantation (trophectoderm [TE]) and early postimplantation (ectoplacental cone [EPC]) placenta precursors, which is associated with later changes in placenta development and function. Sphingolipid metabolism was markedly altered in the plasma of obese dams very early in pregnancy as was expression of genes related to sphingolipid processing in the early placenta. Upregulation of these pathways inhibits angiogenesis and causes endothelial dysfunction. The expression of many other genes related to angiogenesis and vascular development were disrupted in the TE and EPC. Other key changes in the maternal metabolome in obese dams that are likely to influence placenta and fetal development include a marked decrease in myo and chiro-inositol. These early metabolic and gene expression changes may contribute to phenotypic changes in the placenta, as we found that exposure to a high-fat diet decreased placenta microvessel density at both mid and late gestation. This is the first study to demonstrate that maternal obesity alters the transcriptome at the earliest stages of murine placenta development.

Summary Sentence

Obesity in a mouse model leads to alterations in the maternal metabolome and early placenta transcriptome as well as changes in vascularity later in gestation which may provide a mechanism for decreased fetal growth.

© The Author(s) 2018. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com
Tami J. Stuart, Kathleen O'Neill, David Condon, Issac Sasson, Payel Sen, Yunwei Xia, and Rebecca A. Simmons "Diet-induced obesity alters the maternal metabolome and early placenta transcriptome and decreases placenta vascularity in the mouse ," Biology of Reproduction 98(6), 795-809, (18 January 2018). https://doi.org/10.1093/biolre/ioy010
Received: 28 August 2017; Accepted: 17 January 2018; Published: 18 January 2018
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