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

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.

RNA-seq analysis for detecting quantitative trait-associated genes

“…Many RNA-seq based DEG analyses have restrictively compared two or more groups; only a few applications for observing significant genes using quantitative trait is proposed in RNA-seq study. For example, body size can be defined by height and waist circumference instead of ‘small’ and ‘big’ group variables 11 12 . Also, in the research of finding significantly related genes for drug dosage, degree of obesity hormone density, etc., raw quantitative traits can be utilized instead of converted group variables.…”

“…For this reason, many RNA-seq studies still have focused on the relationship between gene expression and experimental conditions regardless of the genetic effects. Hence, the current trend in RNA-seq analysis is to convert quantitative traits as categorical variable based on specific cutoffs, which facilitates the analysis in some practical issues 11 12 13 . However, employing non-converted continuous variables is more advantageous than using converted variables; the greatest advantage is that no within-group phenotypic variation is lost.…”

Impact of maternal obesity on placental transcriptome and morphology associated with fetal growth restriction in mice

“…Changes in placental function are thought to be pivotal in the development of pregnancy complications [10,11] and could also be a key link between the maternal and intrauterine milieu and long-term health of the offspring [12,13]. Alterations in placental function and structure in response to obesity and their underlying molecular mechanisms have been explored both in humans and in animal models [9,[14][15][16][17]]. Yet, even though fetal growth restriction (FGR) is recognized as a placenta-related disorder [18], the impact of maternal obesity on the placental transcriptome in this context remains largely unknown.…”

De novo characterization of placental transcriptome in the Eurasian beaver (Castor fiber L.)

“…Although the placenta is an object of varied studies, most are focused on relationships with human diseases (Cox et al 2011 ; Sitras et al 2015 ), but rarely concern model organisms (Du et al 2014 ; Saben et al 2014 ). Physiological development and proper function of the placenta are under influence of sophisticated pathways related with expression of substantial genes throughout pregnancy.…”