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

Author
item SABEN, JESSICA - Washington University School Of Medicine
item KANG, PING - Arkansas Children'S Nutrition Research Center (ACNC)
item ZHONG, YING - Arkansas Children'S Nutrition Research Center (ACNC)
item THAKALI, KESHARI - Arkansas Children'S Nutrition Research Center (ACNC)
item GOMEZ-ACEVEDO, HORACIO - Arkansas Children'S Nutrition Research Center (ACNC)
item BORENGASSER, SARAH - University Of Denver
item ANDRES, ALINE - Arkansas Children'S Nutrition Research Center (ACNC)
item BADGER, THOMAS - Arkansas Children'S Nutrition Research Center (ACNC)
item SHANKAR, KARTIK - Arkansas Children'S Nutrition Research Center (ACNC)

Submitted to: Placenta
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/22/2014
Publication Date: 12/1/2014
Citation: Saben, J., Kang, P., Zhong, Y., Thakali, K., Gomez-Acevedo, H., Borengasser, S.J., Andres, A., Badger, T.M., Shankar, K. 2014. RNA-seq analysis of the rat placentation site reveals maternal obesity-associated changes in placental and offspring thyroid hormone signaling. Placenta. 35(12):1013-1020.

Interpretive Summary: Childhood obesity is an increasing problem in the US and worldwide. While it is commonly known that diet and exercise are contributing factors to the increasing incidence of obesity, there is also likely a genetic component to obesity that can be passed down from parents to children. The goal of our research is to determine if and how mom’s weight can affect their baby’s gene expression profile and their likelihood of becoming overweight or obese later on in life. We used a rodent model of maternal obesity and examined gene expression profiles in the fetal placenta, fetal liver and weanling offspring. We identified changes in thyroid hormone-related genes to be decreased by maternal obesity, suggesting that lower thyroid hormone expression may account for lower energy metabolism and the increased incidence of obesity in animals born to obese mothers.

Technical Abstract: 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 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. Results and Discussion 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, 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 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.