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性别、父本品种及胎儿体重变化背景下胎儿血浆代谢组的遗传调控与变异

Genetic regulation and variation of fetal plasma metabolome in the context of sex, paternal breeds and variable fetal weight.

作者信息

Ponsuksili Siriluck, Murani Eduard, Fuchs Beate, Galuska Christina E, Reyer Henry, Iqbal Muhammad Arsalan, Li Shuaichen, Oster Michael, Wimmers Klaus

机构信息

Genetics and Genomics, Research Institute for Farm Animal Biology (FBN), Dummerstorf 18196, Germany.

Core Facility Metabolomics, Research Institute for Farm Animal Biology (FBN), Dummerstorf 18196, Germany.

出版信息

Open Biol. 2025 Mar;15(3):240285. doi: 10.1098/rsob.240285. Epub 2025 Mar 5.

DOI:10.1098/rsob.240285
PMID:40037532
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12105786/
Abstract

Metabolic processes in fetuses can significantly influence piglet weight at birth. Understanding the genetic determinants of systemic metabolism is crucial for uncovering how genetic and molecular pathways impact biological mechanisms, particularly during the fetal phase. We present data on 1112 plasma metabolites using untargeted ultra-high performance liquid chromatography-tandem mass spectrometry methods, of 260 backcross (BC) fetuses from two sires' breeds at 63 days post-conception. Eight chemical superclasses have been identified, with lipids accounting for the majority of metabolites. Genomic heritability (h²) was estimated for each metabolite, revealing that 50% had h² values below 0.2, with a higher average in the amino acid class compared with the lipid. We annotated 448 significant metabolite quantitative trait loci associated with 10 metabolites, primarily lipids, indicating strong genetic regulation. Additionally, metabolite associations with sex, fetal weight and sire's breed were explored, revealing significant associations for 354 metabolites. Fetal weight influenced the largest number of metabolites, particularly glycerophospholipids and sphingolipids, emphasizing the genetic and metabolic complexity underlying fetal development. These findings enhance our understanding of the genetic regulation of metabolite levels and their associations with key phenotypic traits in fetuses, providing insights into metabolic pathways, potential biomarkers and serving as a baseline dataset for metabolomics studies of fetuses.

摘要

胎儿的代谢过程会显著影响仔猪出生时的体重。了解全身代谢的遗传决定因素对于揭示基因和分子途径如何影响生物学机制至关重要,尤其是在胎儿期。我们使用非靶向超高效液相色谱-串联质谱法,对受孕63天后来自两个父本品种的260只回交(BC)胎儿的1112种血浆代谢物进行了分析。已鉴定出八个化学超类,其中脂质占代谢物的大部分。对每种代谢物估计了基因组遗传力(h²),结果显示50%的h²值低于0.2,氨基酸类的平均遗传力高于脂质类。我们注释了与10种代谢物相关的448个显著代谢物数量性状位点,主要是脂质,表明存在强大的遗传调控。此外,还探索了代谢物与性别、胎儿体重和父本品种的关联,发现354种代谢物存在显著关联。胎儿体重影响的代谢物数量最多,尤其是甘油磷脂和鞘脂,这强调了胎儿发育背后的遗传和代谢复杂性。这些发现增进了我们对胎儿代谢物水平的遗传调控及其与关键表型特征关联的理解,为代谢途径、潜在生物标志物提供了见解,并作为胎儿代谢组学研究的基线数据集。

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WebGestalt 2024: faster gene set analysis and new support for metabolomics and multi-omics.WebGestalt 2024:更快的基因集分析以及对代谢组学和多组学的新支持。
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Low-input lipidomics reveals lipid metabolism remodelling during early mammalian embryo development.
低投入脂质组学揭示了早期哺乳动物胚胎发育过程中的脂质代谢重塑。
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