Deletion of the Imprinted Phlda2 Gene Increases Placental Passive Permeability in the Mouse.
Deletion of the Imprinted Phlda2 Gene Increases Placental Passive Permeability in the Mouse.
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DOI：
10.3390/genes12050639
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发表时间：
2021-04-25
期刊：
影响因子：
3.5
通讯作者：
Constância M
中科院分区：
文献类型：
--
作者：
Angiolini E;Sandovici I;Coan PM;Burton GJ;Sibley CP;Fowden AL;Constância M
基因组印记是一种表观遗传现象，它导致一小部分基因以特定于父母的方式表达，被认为是与胎盘形成共同进化的。许多印记基因在胎盘中表达，它们在发育和营养供应功能中发挥着不同的作用。然而，只有少数印迹基因被功能测试与交换迷宫区的结构特征有关的营养转移能力的作用。在这里，我们检查了缺乏母体表达的Phlda2基因的小鼠模型的转移能力，这会导致胎盘过度生长和胎儿生长一过性减慢。利用体视学方法，我们发现Phlda2−/+突变体的迷宫区在E16和E19时形态正常。在体内，放射性标记的溶质14C-甲基-D-葡萄糖和14C-MeAIB的胎盘转运在这两个妊娠时间点都不受影响。然而，使用两种惰性亲水性溶质(14C-甘露醇和14C-菊粉)测量的胎盘被动通透性在突变体中显著更高。重要的是，这种被动通透性的增加与胎儿的追赶生长有关。我们的发现揭示了印记的Phlda2基因在改变胎盘被动通透性方面发挥的关键作用，这可能对决定胎儿生长至关重要。
Genomic imprinting, an epigenetic phenomenon that causes the expression of a small set of genes in a parent-of-origin-specific manner, is thought to have co-evolved with placentation. Many imprinted genes are expressed in the placenta, where they play diverse roles related to development and nutrient supply function. However, only a small number of imprinted genes have been functionally tested for a role in nutrient transfer capacity in relation to the structural characteristics of the exchange labyrinthine zone. Here, we examine the transfer capacity in a mouse model deficient for the maternally expressed Phlda2 gene, which results in placental overgrowth and a transient reduction in fetal growth. Using stereology, we show that the morphology of the labyrinthine zone in Phlda2−/+ mutants is normal at E16 and E19. In vivo placental transfer of radiolabeled solutes 14C-methyl-D-glucose and 14C-MeAIB remains unaffected at both gestational time points. However, placental passive permeability, as measured using two inert hydrophilic solutes (14C-mannitol; 14C-inulin), is significantly higher in mutants. Importantly, this increase in passive permeability is associated with fetal catch-up growth. Our findings uncover a key role played by the imprinted Phlda2 gene in modifying placental passive permeability that may be important for determining fetal growth.
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影响因子：
--
作者：
Janssen AB;Tunster SJ;Heazell AE;John RM
通讯作者：
John RM
DOI：
10.1016/j.ajpath.2018.07.027
发表时间：
2018-12
期刊：
The American journal of pathology
影响因子：
--
作者：
Nuzzo AM;Camm EJ;Sferruzzi-Perri AN;Ashmore TJ;Yung HW;Cindrova-Davies T;Spiroski AM;Sutherland MR;Logan A;Austin-Williams S;Burton GJ;Rolfo A;Todros T;Murphy MP;Giussani DA
通讯作者：
Giussani DA
影响因子：
3.8
作者：
McMinn, J.;Wei, M.;Tycko, B.
通讯作者：
Tycko, B.
影响因子：
3.8
作者：
Angiolini, E;Fowden, A;Constância, M
通讯作者：
Constância, M
影响因子：
3.8
作者：
Carter, AM
通讯作者：
Carter, AM