Placental Transcriptome Adaptations to Maternal Nutrient Restriction in Sheep.

Placental Transcriptome Adaptations to Maternal Nutrient Restriction in Sheep.
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DOI:
10.3390/ijms22147654
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发表时间:
2021-07-17
影响因子:
5.6
通讯作者:
Satterfield MC
Satterfield MC
中科院分区:
生物学2区
文献类型:
--
作者:
Steinhauser CB;Lambo CA;Askelson K;Burns GW;Behura SK;Spencer TE;Bazer FW;Satterfield MC

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胎盘的发育是根据母体营养限制(NR)而改变的,从而导致胎儿生长速率的谱。在妊娠第35-135天,采用国家研究委员会(NRC)推荐摄入量的100% (n = 8)或50% (NR; n = 28)饲喂单胎妊娠绵羊,以阐明第70天和第135天胎盘组转录组的改变。根据第135天胎儿体重,将NR胎儿进一步分为上四分位数(NR NonSGA, n = 7)和下四分位数(NR SGA, n = 7)。在妊娠第70天时,NR SGA与100% NRC放置物间有22个基因表达异常,NR NonSGA与100% NRC放置物间有27个基因表达异常,NR SGA与NR NonSGA放置物间有22个基因表达异常。这些基因介导分子功能,如MHC II类蛋白结合、信号受体结合和细胞因子活性。基因集富集分析(GSEA)显示,天然杀伤细胞介导的细胞毒性基因在NR SGA中明显高于100%的NRC放置物,并且在第70天,NR SGA和NR NonSGA放置物之间的营养利用途径发生了变化。结果确定了与SGA胎鼠功能受损相关的新因素,以及NR非SGA胎鼠适应营养困难的潜力。
Placental development is modified in response to maternal nutrient restriction (NR), resulting in a spectrum of fetal growth rates. Pregnant sheep carrying singleton fetuses and fed either 100% (n = 8) or 50% (NR; n = 28) of their National Research Council (NRC) recommended intake from days 35–135 of pregnancy were used to elucidate placentome transcriptome alterations at both day 70 and day 135. NR fetuses were further designated into upper (NR NonSGA; n = 7) and lower quartiles (NR SGA; n = 7) based on day 135 fetal weight. At day 70 of pregnancy, there were 22 genes dysregulated between NR SGA and 100% NRC placentomes, 27 genes between NR NonSGA and 100% NRC placentomes, and 22 genes between NR SGA and NR NonSGA placentomes. These genes mediated molecular functions such as MHC class II protein binding, signaling receptor binding, and cytokine activity. Gene set enrichment analysis (GSEA) revealed significant overrepresentation of genes for natural-killer-cell-mediated cytotoxicity in NR SGA compared to 100% NRC placentomes, and alterations in nutrient utilization pathways between NR SGA and NR NonSGA placentomes at day 70. Results identify novel factors associated with impaired function in SGA placentomes and potential for placentomes from NR NonSGA pregnancies to adapt to nutritional hardship.
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