Maternal Pre-Pregnancy Obesity Is Associated with Altered Placental Transcriptome

Abstract

Maternal obesity has a major impact on pregnancy outcomes. There is growing evidence that maternal obesity has a negative influence on placental development and function, thereby adversely influencing offspring programming and health outcomes. However, the molecular mechanisms underlying these processes are poorly understood. We analysed ten term placenta’s whole transcriptomes in obese (n = 5) and normal weight women (n = 5), using the Affymetrix microarray platform. Analyses of expression data were carried out using non-parametric methods. Hierarchical clustering and principal component analysis showed a clear distinction in placental transcriptome between obese and normal weight women. We identified 72 differentially regulated genes, with most being down-regulated in obesity (n = 61). Functional analyses of the targets using DAVID and IPA confirm the dysregulation of previously identified processes and pathways in the placenta from obese women, including inflammation and immune responses, lipid metabolism, cancer pathways, and angiogenesis. In addition, we detected new molecular aspects of obesity-derived effects on the placenta, involving the glucocorticoid receptor signalling pathway and dysregulation of several genes including CCL2, FSTL3, IGFBP1, MMP12, PRG2, PRL, QSOX1, SERPINE2 and TAC3. Our global gene expression profiling approach demonstrates that maternal obesity creates a unique in utero environment that impairs the placental transcriptome.

Association between maternal overweight or obesity and cerebral palsy in children: A meta-analysis

“…Another mechanism by which maternal obesity may affect the neurodevelopment of offspring may be related to insulin resistance, which contributes to abnormal central glucose metabolism and transport. One study[ 46 ] analyzed the whole placental transcriptome in obese and normal-weight women and showed that maternal obesity had a negative effect on placental development and function. Another study[ 47 ] used oxidative stress biomarkers to analyze samples from mothers and offspring and found that maternal obesity could affect the maternal microenvironment and that oxidative stress has a negative impact on the placenta and fetal growth.…”

Impact of pregravid obesity on maternal and fetal immunity: Fertile grounds for reprogramming

“…A successful pregnancy involves complex interactions between the immune cells residing at the maternal-fetal interface 108 and circulating maternal factors that could culminate into secretion of immune mediators into fetal circulation. 109,110 During the first trimester, the placenta enables the establishment of pregnancy, providing physical support and immunologic tolerance to the developing embryo. 111 As gestation progresses, the placenta takes over the roles of facilitating gas exchange as well as the transfer of nutrients, waste products, hormones, and other immune mediator that support fetal growth and impact development and maturation of the offspring immune system.…”

“…The fetal portion of the placenta is called the villous chorion, which allows for the transfer of nutrients from maternal blood to fetal circulation. A successful pregnancy involves complex interactions between the immune cells residing at the maternal–fetal interface and circulating maternal factors that could culminate into secretion of immune mediators into fetal circulation . During the first trimester, the placenta enables the establishment of pregnancy, providing physical support and immunologic tolerance to the developing embryo .…”

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.…”