4.5 Article

RNA-seq analysis of the rat placentation site reveals maternal obesity-associated changes in placental and offspring thyroid hormone signaling

期刊

PLACENTA
卷 35, 期 12, 页码 1013-1020

出版社

W B SAUNDERS CO LTD
DOI: 10.1016/j.placenta.2014.09.015

关键词

Metabolism; Obesity; Placenta; RNA-seq; Thyroid hormone; Uncoupling proteins

资金

  1. National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases [R01-DK084225]
  2. USDA Agriculture Research Service [CRIS 6251-51000-007-04S]
  3. UAMS Translational Research Institute - National Institutes of Health Clinical and Translational Science Award (CTSA) program [UL1TR000039, KL2TR000063]

向作者/读者索取更多资源

Introduction: In animal models, maternal obesity (OB) leads to augmented risk of offspring OB. While placental function is influenced by maternal habitus, the effect of maternal obesity on the interacting zones of the placenta [the labyrinth (LZ), junctional (JZ) and metrial gland (MG)] remains unknown. Methods: Using a rat maternal obesity model, we conducted transcriptomic profiling of the uteroplacental compartments and fetal liver (FL) at dpc 18.5, in conjunction with analyses of mRNA expression of key thyroid hormone (TH) signaling genes in the placenta, fetus and weanling offspring. Results and Discussion: Gene expression analysis of placenta and offspring revealed that each uteroplacental compartment responds distinctly to maternal OB with changes in inflammatory signaling, lipid metabolism and hormone stimulus being the predominant effects. OB-induced alterations in 17 genes were confirmed by qPCR, including reductions in thyrotropin-releasing hormone (Trh) in JZ. We further characterized mRNA and protein expression of TH signaling regulators including deiodinases (Dio), TH receptors (Tr), and downstream targets (uncoupling proteins (14)). A concerted down-regulation of multiple facets of thyroid hormone signaling in the JZ and FL was observed. JZ expression of thyroid hormone signaling components Trh, Dio2, Tr alpha, and Ucp2 were negatively associated with maternal leptin. mRNA expression of TRH, TR beta and UCP1 were also decreased in term placenta from OB women. Finally, our studies identified persistent impairments in expression of TH related genes in tissues from offspring of obese dams. Conclusions: The role of lower placental thyroid expression is worthy of further study

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