背景:宫内感染早产是新生儿神经系统疾病的主要原因。同样,母亲肥胖与羊膜腔感染和炎症相关.孕妇肥胖是否是早产引起胎儿脑损伤的危险因素尚不清楚。这项研究假设,在早产的情况下,母亲肥胖会加剧胎儿神经炎症。
目的:本研究旨在利用小鼠模型研究母亲肥胖对早产引起的围产期神经炎症反应的影响。
方法:肥胖的大坝是通过在整个怀孕期间维持的高脂肪饮食产生的。并行,无肥胖(正常)的水坝接受控制饮食。所有水坝都与正常饮食的雄性配对。在通常为19至21天妊娠的胚胎第15.5天,妊娠母鼠被随机分配接受细菌内毒素(脂多糖)或媒介物(磷酸盐缓冲盐水)的宫内给药。宫内给药后6小时收集胎儿大脑,和关键炎症细胞因子的表达(Il1b,Il6和Tnf)和代谢面板,免疫,和炎症基因进行了分析。
结果:用磷酸盐缓冲盐水,与母亲肥胖相关的基因表达没有差异。肥胖大坝与接受脂多糖的正常大坝相比,胎儿大脑中的Il6和免疫/炎症表达谱存在实质性差异。在这些条件下检查的代谢基因之间几乎没有观察到差异。与母亲肥胖相关的基因表达模式与白质损伤相关的通路相关。
结论:细菌内毒素通过宫内脂多糖引起的神经炎症标志物在肥胖母鼠胚胎脑中的表达更高。表达谱表明,与宫内炎症相结合,母亲肥胖可能增加胎儿白质损伤的风险。需要进一步调查以了解与早产相关的孕产妇健康与神经系统结局之间的关系。
BACKGROUND: Preterm birth from intrauterine infection is a leading cause of neonatal neurologic morbidity. Likewise, maternal obesity is associated with intra-amniotic infection and inflammation. Whether maternal obesity is a risk factor for fetal brain injury that occurs with premature birth remains unknown. This study hypothesized that maternal obesity intensifies fetal neuroinflammation in the setting of premature delivery.
OBJECTIVE: This study aimed to examine the influence of maternal obesity on perinatal neuroinflammatory responses that arise with preterm birth using a murine model.
METHODS: Dams with obesity were generated via a high-fat diet that was maintained throughout pregnancy. In parallel, dams without obesity (normal) received a control diet. All dams were paired with males on normal diet. Pregnant dams were randomized to receive an intrauterine administration of bacterial endotoxin (lipopolysaccharide) or the vehicle (phosphate-buffered saline) on embryo day 15.5 of what is typically a 19- to 21-day gestation. Fetal brains were harvested 6 hours after intrauterine administrations, and the expressions of key inflammatory cytokines (Il1b, Il6, and Tnf) and panels of metabolic, immune, and inflammatory genes were analyzed.
RESULTS: With the phosphate-buffered saline, there was no difference in gene expression related to maternal obesity. There were substantial differences in Il6 and immune/inflammatory expression profiles in fetal brains from dams with obesity vs normal dams that received lipopolysaccharide. Few differences were observed among the metabolic genes examined under these conditions. The gene expression pattern associated with maternal obesity correlated with pathways related to white matter injury.
CONCLUSIONS: The expression of neuroinflammatory markers instigated by bacterial endotoxin via intrauterine lipopolysaccharide was greater in embryo brains obtained from dams with obesity. Expression profiles suggest that in combination with intrauterine inflammation, maternal obesity may increase the risk of fetal white matter injury. Further investigation is warranted to understand the relationship between maternal health and neurologic outcomes associated with prematurity.