Malik Sajida, Diot Alan, Morten Karl, Dombi Eszter, Vatish Manu, Boyd C A Richard, Poulton Joanna
Nuffield Department of Obstetrics and Gynaecology, University of Oxford, Oxford, UK.
Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK.
Oncotarget. 2017 Nov 25;8(65):109478-109486. doi: 10.18632/oncotarget.22695. eCollection 2017 Dec 12.
Exposure to maternal malnutrition impairs postnatal health. Acute nutritional stress is less clearly implicated in intrauterine programming. We studied the effects of stressing pregnant mothers on perinatal growth and adult glucose homeostasis. We compared one group ("stressed", mothers fasted for 16 hours) with controls ("unstressed"). We found that fasting stress had adverse effects on the weight of the fetuses conceived (<0.005) and the placental efficiency (<0.001) in stressed compared to unstressed offspring. Placental weight was increased (<0.001) presumably in compensation. Stress affected the glucose homeostasis of the offspring when they became adults (<0.005) when analysed as individuals. We previously linked nutritional stress throughout pregnancy with a mitochondrial stress response. We modelled placenta with cultured human trophoblast cells (BeWos) and fetal tissues with mouse embryonic fibroblasts (MEFs). High throughput imaging showed that the mitochondria of both cell types underwent a similar sequence of changes in morphology, induced by nutritional stresses. The contrasting stress responses on fetal and placental weight were not captured by the cellular models. The stress of maternal fasting may be an important determinant of perinatal outcome in the mouse and might be relevant to nutritional stress in human pregnancy.
孕期母亲营养不良会损害产后健康。急性营养应激与宫内编程的关联尚不明确。我们研究了给怀孕母亲施加应激对围产期生长和成年后葡萄糖稳态的影响。我们将一组（“应激组”，母亲禁食16小时）与对照组（“非应激组”）进行了比较。我们发现，与非应激组后代相比，禁食应激对应激组受孕胎儿的体重（<0.005）和胎盘效率（<0.001）有不利影响。胎盘重量增加（<0.001），可能是一种代偿。当作为个体进行分析时，应激会影响后代成年后的葡萄糖稳态（<0.005）。我们之前将整个孕期的营养应激与线粒体应激反应联系起来。我们用培养的人滋养层细胞（BeWos）模拟胎盘，用小鼠胚胎成纤维细胞（MEFs）模拟胎儿组织。高通量成像显示，两种细胞类型的线粒体在营养应激诱导下经历了相似的形态变化序列。细胞模型未体现出对胎儿和胎盘重量的不同应激反应。母体禁食应激可能是小鼠围产期结局的一个重要决定因素，可能与人类孕期的营养应激有关。
