背景:妊娠期肥胖与不良母婴结局有关。这些结果涉及的因素可能包括母体胰岛素抵抗增加,炎症,氧化应激,和营养处理不当。胎盘是胎儿结局的主要决定因素,其功能可能受到母亲肥胖的影响。这项研究的目的是确定肥胖对母体脂质处理的影响,炎症和氧化还原状态,胎盘氧化应激,炎症信号,和相对于女性和男性胎儿生长的基因表达。
方法:从9周前开始,给雌性小鼠喂食对照或生性高脂肪/高糖饮食(HFHS),在这期间,怀孕。在怀孕的第18.5天,母体血浆,还有肝脏,胎盘,收集胎儿血清以检查免疫和氧化还原状态。解剖胎盘迷宫区(Lz)用于基因表达变化的RNA测序分析。
结果:HFHS饮食诱导,在水坝里,肝脂肪变性,氧化应激(过氧化氢酶减少,蛋白质氧化升高)和促炎途径(p38-MAPK)的激活,以及不平衡的循环细胞因子浓度(增加的IL-6和减少的IL-5和IL-17A)。HFHS胎儿不对称生长受限,显示循环细胞因子的性别特异性变化(GM-CSF,TNF-α,IL-6和IFN-γ)。通过HFHS饮食改变胎盘Lz的形态,与氧化应激相关的基因和蛋白质表达的性别特异性改变有关,炎症,和压力信号。胎盘基因表达变化与宫内炎症模型中看到的相当,并且与涉及转录因子的转录网络有关,LYL1和PLAG1。
结论:这项研究表明,母亲肥胖的胎儿生长受限与氧化应激升高有关,炎症途径,和性别特异性胎盘变化。我们的数据很重要,考虑到明显的后果和全球肥胖率的上升。
BACKGROUND: Obesity during pregnancy is related to adverse maternal and neonatal outcomes. Factors involved in these outcomes may include increased maternal insulin resistance, inflammation, oxidative stress, and nutrient mishandling. The placenta is the primary determinant of fetal outcomes, and its function can be impacted by maternal obesity. The aim of this study on mice was to determine the effect of obesity on maternal lipid handling, inflammatory and redox state, and placental oxidative stress, inflammatory signaling, and gene expression relative to female and male fetal growth.
METHODS: Female mice were fed control or obesogenic high-fat/high-sugar diet (HFHS) from 9 weeks prior to, and during, pregnancy. On day 18.5 of pregnancy, maternal plasma, and liver, placenta, and fetal serum were collected to examine the immune and redox states. The placental labyrinth zone (Lz) was dissected for RNA-sequencing analysis of gene expression changes.
RESULTS: the HFHS diet induced, in the dams, hepatic steatosis, oxidative stress (reduced catalase, elevated protein oxidation) and the activation of pro-inflammatory pathways (p38-MAPK), along with imbalanced circulating cytokine concentrations (increased IL-6 and decreased IL-5 and IL-17A). HFHS fetuses were asymmetrically growth-restricted, showing sex-specific changes in circulating cytokines (GM-CSF, TNF-α, IL-6 and IFN-γ). The morphology of the placenta Lz was modified by an HFHS diet, in association with sex-specific alterations in the expression of genes and proteins implicated in oxidative stress, inflammation, and stress signaling. Placental gene expression changes were comparable to that seen in models of intrauterine inflammation and were related to a transcriptional network involving transcription factors, LYL1 and PLAG1.
CONCLUSIONS: This study shows that fetal growth restriction with maternal obesity is related to elevated oxidative stress, inflammatory pathways, and sex-specific placental changes. Our data are important, given the marked consequences and the rising rates of obesity worldwide.