title: RNA-seq analysis of the rat placentation site reveals maternal obesity-associated changes in placental and offspring thyroid hormone signaling.
abstract: BACKGROUND
  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 utero-placental 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.
  
  
  CONCLUSIONS
  Gene expression analysis of placenta and offspring revealed that each utero-placental 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 (Ucp)). 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, Trα, and Ucp2 were negatively associated with maternal leptin. mRNA expression of TRH, TRβ 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 as a possible pathway that leads to low energy metabolism and obesity in animals born to obese mothers.
authors.affiliation: Arkansas Children's Nutrition Center, University of Arkansas for Medical Sciences, Little Rock, AR, USA; Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA; Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: J
authors.initials: J
authors.lastname: Saben
authors.affiliation: Arkansas Children's Nutrition Center, University of Arkansas for Medical Sciences, Little Rock, AR, USA; Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
authors.forename: P
authors.initials: P
authors.lastname: Kang
authors.affiliation: Arkansas Children's Nutrition Center, University of Arkansas for Medical Sciences, Little Rock, AR, USA; Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhong
authors.affiliation: Arkansas Children's Nutrition Center, University of Arkansas for Medical Sciences, Little Rock, AR, USA; Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
authors.forename: K M
authors.initials: KM
authors.lastname: Thakali
authors.affiliation: Arkansas Children's Nutrition Center, University of Arkansas for Medical Sciences, Little Rock, AR, USA; Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
authors.forename: H
authors.initials: H
authors.lastname: Gomez-Acevedo
authors.affiliation: Arkansas Children's Nutrition Center, University of Arkansas for Medical Sciences, Little Rock, AR, USA; Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
authors.forename: S J
authors.initials: SJ
authors.lastname: Borengasser
authors.affiliation: Arkansas Children's Nutrition Center, University of Arkansas for Medical Sciences, Little Rock, AR, USA; Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
authors.forename: A
authors.initials: A
authors.lastname: Andres
authors.affiliation: Arkansas Children's Nutrition Center, University of Arkansas for Medical Sciences, Little Rock, AR, USA; Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
authors.forename: T M
authors.initials: TM
authors.lastname: Badger
authors.affiliation: Arkansas Children's Nutrition Center, University of Arkansas for Medical Sciences, Little Rock, AR, USA; Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA. Electronic address: ShankarKartik@uams.edu.
authors.forename: K
authors.initials: K
authors.lastname: Shankar
mesh_terms: D000818:Animals; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008099:Liver / Q000378:metabolism*; D039382:Maternal Nutritional Physiological Phenomena / Q000502:physiology*; D009765:Obesity / Q000378:metabolism*; D010920:Placenta / Q000378:metabolism*; D010929:Placentation / Q000235:genetics*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000235:genetics; D013963:Thyroid Hormones / Q000378:metabolism*; D059467:Transcriptome
chemical_list: D013963:Thyroid Hormones
keywords: Metabolism; Obesity; Placenta; RNA-seq; Thyroid hormone; Uncoupling proteins