A co-ordinated transcriptional programme in the maternal liver supplies LC-PUFAs to the conceptus using phospholipids
A co-ordinated transcriptional programme in the maternal liver supplies LC-PUFAs to the conceptus using phospholipids
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DOI：
10.1101/2023.06.23.546226
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发表时间：
2023-06
期刊：
影响因子：
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通讯作者：
Risha Amarsi;S. Furse;M. A. Cleaton;Sarah Maurel;Alice L Mitchell;A. Ferguson-Smith;N. Cenac;C. Williamson;A. Koulman;M. Charalambous
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文献类型：
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作者：
Risha Amarsi;S. Furse;M. A. Cleaton;Sarah Maurel;Alice L Mitchell;A. Ferguson-Smith;N. Cenac;C. Williamson;A. Koulman;M. Charalambous
必需脂肪酸（EFA）及其衍生物，即长链和极长链多不饱和脂肪酸（LC-PUFA），优先由母体转运至胎儿。无法提供EFA与死胎、胎儿生长受限和神经发育不良密切相关。然而，怀孕期间的膳食补充剂不能简单地逆转这些结果，这表明膳食EFA摄入量和母体供应的分子机制之间的相互作用还不完全清楚。在这里，我们将联合收割机非靶向脂质组学与健康和遗传操作小鼠模型的转录谱分析相结合，以了解向发育中的胎儿提供LC-PUFA所需的母体适应性。我们发现了晚期妊娠特异性的肝X受体信号通路的选择性激活，其显著增加了循环磷脂中LC-PUFA的母体供应。至关重要的是，在母亲中遗传消除这一途径减少了胎儿的LC-PUFA积累。总的来说，我们的工作提出了新的分子策略，以改善这些重要的脂质的母胎转移。
Essential fatty acids (EFAs) and their derivatives, the long and very long chain polyunsaturated fatty acids (LC-PUFAs), are preferentially transported by the mother to the fetus. Failure to supply EFAs is strongly linked with stillbirth, fetal growth restriction, and impaired neurodevelopmental outcomes. However, dietary supplementation during pregnancy is unable to simply reverse these outcomes, suggesting imperfectly understood interactions between dietary EFA intake and the molecular mechanisms of maternal supply. Here we combine untargeted lipidomics with transcriptional profiling of healthy and genetically-manipulated murine models to understand the maternal adaptations required to provide LC-PUFAs to the developing fetus. We discovered a late pregnancy-specific, selective activation of the Liver X Receptor signalling pathway which dramatically increases maternal supply of LC-PUFAs within circulating phospholipids. Crucially, genetic ablation of this pathway in the mother reduced LC-PUFA accumulation by the fetus. Overall our work suggests new molecular strategies for improving maternal-fetal transfer of these important lipids.