Centre for Trophoblast Research, Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK.
Department for the Woman and Newborn Health Promotion, Universidad de Chile, Santiago, Chile.
Acta Physiol (Oxf). 2022 Oct;236(2):e13861. doi: 10.1111/apha.13861. Epub 2022 Aug 3.
Diets containing high-fat and high sugar (HFHS) lead to overweight/obesity. Overweight/obesity increases the risk of infertility, and of the pregnant mother and her child for developing metabolic conditions. Overweight/obesity has been recreated in mice, but most studies focus on the effects of chronic, long-term HFHS diet exposure. Here, we exposed mice to HFHS from 3 weeks prior to pregnancy with the aim of determining impacts on fertility, and gestational and neonatal outcomes.
Time-domain NMR scanning was used to assess adiposity, glucose, and insulin tolerance tests were employed to examine metabolic physiology, and morphological and proteomic analyses conducted to assess structure and nutrient levels of maternal organs and placenta.
Fertility measures of HFHS dams were largely the same as controls. HFHS dams had increased adiposity pre-pregnancy, however, exhibited exacerbated lipolysis/hyper-mobilization of adipose stores in late pregnancy. While there were no differences in glucose or insulin tolerance, HFHS dams were hyperglycemic and hyperinsulinemic in pregnancy. HFHS dams had fatty livers and altered pancreatic islet morphology. Although fetuses were hyperglycemic and hyperinsulinemic, there was no change in fetal growth in HFHS dams. There were also reductions in placenta formation. Moreover, there was increased offspring loss during lactation, which was related to aberrant mammary gland development and milk protein composition in HFHS dams.
These findings are relevant given current dietary habits and the development of maternal and offspring alterations in the absence of an increase in maternal weight and adiposity during pregnancy, which are the current clinical markers to determine risk across gestation.
高脂肪高糖（HFHS）饮食会导致超重/肥胖。超重/肥胖会增加不孕、孕妇及其子女患代谢疾病的风险。肥胖已经在小鼠中重现，但大多数研究都集中在慢性、长期 HFHS 饮食暴露的影响上。在这里，我们从怀孕前 3 周开始让小鼠暴露于 HFHS 中，目的是确定其对生育能力以及妊娠和新生儿结局的影响。
时域 NMR 扫描用于评估肥胖程度，葡萄糖和胰岛素耐量试验用于检查代谢生理学，形态和蛋白质组学分析用于评估母体器官和胎盘的结构和营养水平。
HFHS 母鼠的生育力指标与对照组大致相同。HFHS 母鼠在怀孕前就已经肥胖，但是在怀孕后期脂肪分解/脂肪储存过度活跃。尽管葡萄糖和胰岛素耐量没有差异，但 HFHS 母鼠在怀孕期间血糖和胰岛素水平升高。HFHS 母鼠的肝脏脂肪变性和胰岛形态改变。尽管胎儿血糖和胰岛素水平升高，但 HFHS 母鼠的胎儿生长没有变化。胎盘形成也减少。此外，哺乳期的后代死亡率增加，这与 HFHS 母鼠的乳腺发育异常和乳蛋白组成有关。
鉴于目前的饮食习惯以及在怀孕期间母体体重和肥胖程度没有增加的情况下母体和后代的变化，这些发现具有相关性，目前的临床标志物是在整个孕期确定风险的依据。
