Altmäe Signe, Segura Maria Teresa, Esteban Francisco J, Bartel Sabine, Brandi Pilar, Irmler Martin, Beckers Johannes, Demmelmair Hans, López-Sabater Carmen, Koletzko Berthold, Krauss-Etschmann Susanne, Campoy Cristina
Department of Women's and Children's Health, Division of Obstetrics and Gynecology, Karolinska Institutet, Stockholm, Sweden.
Centre of Excellence for Paediatric Research EURISTIKOS and Department of Paediatrics, School of Medicine, University of Granada, Granada, Spain.
PLoS One. 2017 Jan 26;12(1):e0169223. doi: 10.1371/journal.pone.0169223. eCollection 2017.
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.
孕妇肥胖对妊娠结局有重大影响。越来越多的证据表明，孕妇肥胖对胎盘发育和功能有负面影响，从而对后代的编程和健康结局产生不利影响。然而，这些过程背后的分子机制却知之甚少。我们使用Affymetrix微阵列平台分析了肥胖（n = 5）和体重正常（n = 5）女性的10个足月胎盘的全转录组。使用非参数方法对表达数据进行分析。层次聚类和主成分分析表明，肥胖和体重正常女性的胎盘转录组存在明显差异。我们鉴定出72个差异调节基因，其中大多数在肥胖中下调（n = 61）。使用DAVID和IPA对这些靶点进行功能分析，证实了肥胖女性胎盘中先前确定的过程和途径的失调，包括炎症和免疫反应、脂质代谢、癌症途径和血管生成。此外，我们检测到肥胖对胎盘产生影响的新分子层面，涉及糖皮质激素受体信号通路以及包括CCL2、FSTL3、IGFBP1、MMP12、PRG2、PRL、QSOX1、SERPINE2和TAC3在内的多个基因的失调。我们的全基因表达谱分析方法表明，孕妇肥胖会创造一个独特的子宫内环境，损害胎盘转录组。
