4.8 Article

Fetal and trophoblast PI3K p110α have distinct roles in regulating resource supply to the growing fetus in mice

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ELIFE
卷 8, 期 -, 页码 -

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ELIFE SCIENCES PUBLICATIONS LTD
DOI: 10.7554/eLife.45282

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  1. Centre for Trophoblast Research
  2. Royal Society
  3. European Cooperation in Science and Technology
  4. Erasmus+
  5. BBSRC [BBS/E/B/000C0421] Funding Source: UKRI
  6. MRC [MR/R022690/1, MC_UU_00014/5, MC_UU_00014/4, MC_UU_12012/5] Funding Source: UKRI

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Studies suggest that placental nutrient supply adapts according to fetal demands. However, signaling events underlying placental adaptations remain unknown. Here we demonstrate that phosphoinositide 3-kinase p110 alpha in the fetus and the trophoblast interplay to regulate placental nutrient supply and fetal growth. Complete loss of fetal p110 alpha caused embryonic death, whilst heterozygous loss resulted in fetal growth restriction and impaired placental formation and nutrient transport. Loss of trophoblast p110 alpha resulted in viable fetuses, abnormal placental development and a failure of the placenta to transport sufficient nutrients to match fetal demands for growth. Using RNA-seq we identified genes downstream of p110 alpha in the trophoblast that are important in adapting placental phenotype. Using CRISPR/Cas9 we showed loss of p110 alpha differentially affects gene expression in trophoblast and embryonic stem cells. Our findings reveal important, but distinct roles for p110 alpha in the different compartments of the conceptus, which control fetal resource acquisition and growth.

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