Serpente Patricia, Zhang Ying, Islimye Eva, Hart-Johnson Sarah, Gould Alex P
Laboratory of Physiology and Metabolism, The Francis Crick Institute, London, NW1 1AT, UK.
MRC National Institute for Medical Research, UK, Mill Hill, London, NW7 1AA, UK.
Wellcome Open Res. 2022 May 4;6:218. doi: 10.12688/wellcomeopenres.17124.2. eCollection 2021.
Maternal malnutrition can lead to fetal growth restriction. This is often associated with organ sparing and long-lasting physiological dysfunctions during adulthood, although the underlying mechanisms are not yet well understood. Low protein (LP) dietary models in C57BL/6J mice were used to investigate the proximal effects of maternal malnutrition on fetal organ weights and organ sparing at embryonic day 18.5 (E18.5). Maternal 8% LP diet induced strikingly different degrees of fetal growth restriction in different animal facilities, but adjustment of dietary protein content allowed similar fetal body masses to be obtained. A maternal LP diet that restricted fetal body mass by 40% did not decrease fetal brain mass to the same extent, reflecting positive growth sparing of this organ. Under these conditions, fetal pancreas and liver mass decreased by 60-70%, indicative of negative organ sparing. A series of dietary swaps between LP and standard diets showed that the liver is capable of efficient catch-up growth from as late as E14.5 whereas, after E10.5, the pancreas is not. This study highlights that the reproducibility of LP fetal growth restriction studies between laboratories can be improved by careful calibration of maternal dietary protein content. LP diets that induce 30-40% restriction of prenatal growth provide a good model for fetal organ sparing. For the liver, recovery of growth following protein restriction is efficient throughout fetal development but, for the pancreas, transient LP exposures spanning the progenitor expansion phase lead to an irreversible fetal growth deficit.
母体营养不良会导致胎儿生长受限。这通常与成年期的器官保留和长期生理功能障碍有关，尽管其潜在机制尚未完全明确。在C57BL/6J小鼠中采用低蛋白（LP）饮食模型，以研究母体营养不良在胚胎第18.5天（E18.5）对胎儿器官重量和器官保留的近端影响。母体8% LP饮食在不同动物设施中诱导出程度显著不同的胎儿生长受限，但调整饮食蛋白质含量可使胎儿体重相似。使胎儿体重受限40%的母体LP饮食并未使胎儿脑重减少相同程度，这反映出该器官存在正向生长保留。在这些条件下，胎儿胰腺和肝脏重量减少60 - 70%，表明存在负向器官保留。LP饮食与标准饮食之间的一系列饮食交换表明，肝脏能够从E14.5这么晚的时候开始进行有效的追赶生长，而在E10.5之后，胰腺则不能。本研究强调，通过仔细校准母体饮食蛋白质含量，可提高实验室间LP胎儿生长受限研究的可重复性。诱导产前生长受限30 - 40%的LP饮食为胎儿器官保留提供了一个良好模型。对于肝脏而言，在整个胎儿发育过程中，蛋白质限制后的生长恢复都是有效的，但对于胰腺来说，在祖细胞扩增阶段的短暂LP暴露会导致不可逆的胎儿生长缺陷。
