J Saben1, P Kang2, Y Zhong2, K M Thakali2, H Gomez-Acevedo2, S J Borengasser2, A Andres2, T M Badger2, K Shankar3. 1. 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. 2. 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. 3. 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.
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, 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.
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 ratmaternal 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, Trα, and Ucp2 were negatively associated with maternal leptin. mRNA expression of TRH, TRβ and UCP1 were also decreased in term placenta from OBwomen. 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: Melissa A Suter; Haleh Sangi-Haghpeykar; Lori Showalter; Cynthia Shope; Min Hu; Kathleen Brown; Sarah Williams; R Alan Harris; Kevin L Grove; Robert H Lane; Kjersti M Aagaard Journal: Mol Endocrinol Date: 2012-09-26
Authors: D Farley; M E Tejero; A G Comuzzie; P B Higgins; L Cox; S L Werner; S L Jenkins; C Li; J Choi; E J Dick; G B Hubbard; P Frost; D J Dudley; B Ballesteros; G Wu; P W Nathanielsz; N E Schlabritz-Loutsevitch Journal: Placenta Date: 2009-07-25 Impact factor: 3.481
Authors: Margaret J R Heerwagen; Michael S Stewart; Becky A de la Houssaye; Rachel C Janssen; Jacob E Friedman Journal: PLoS One Date: 2013-06-25 Impact factor: 3.240
Authors: Suhas Sureshchandra; Nicole E Marshall; Randall M Wilson; Tasha Barr; Maham Rais; Jonathan Q Purnell; Kent L Thornburg; Ilhem Messaoudi Journal: Front Physiol Date: 2018-08-07 Impact factor: 4.566
Authors: Daniela de Barros Mucci; Laura C Kusinski; Phoebe Wilsmore; Elena Loche; Lucas C Pantaleão; Thomas J Ashmore; Heather L Blackmore; Denise S Fernandez-Twinn; Maria das Graças T do Carmo; Susan E Ozanne Journal: Int J Obes (Lond) Date: 2020-03-13 Impact factor: 5.095