| First Author | López-Tello J | Year | 2019 |
| Journal | Elife | Volume | 8 |
| PubMed ID | 31241463 | Mgi Jnum | J:290696 |
| Mgi Id | MGI:6443332 | Doi | 10.7554/eLife.45282 |
| Citation | Lopez-Tello J, et al. (2019) Fetal and trophoblast PI3K p110alpha have distinct roles in regulating resource supply to the growing fetus in mice. Elife 8:e45282 |
| abstractText | 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 p110alpha in the fetus and the trophoblast interplay to regulate placental nutrient supply and fetal growth. Complete loss of fetal p110alpha caused embryonic death, whilst heterozygous loss resulted in fetal growth restriction and impaired placental formation and nutrient transport. Loss of trophoblast p110alpha 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 p110alpha in the trophoblast that are important in adapting placental phenotype. Using CRISPR/Cas9 we showed loss of p110alpha differentially affects gene expression in trophoblast and embryonic stem cells. Our findings reveal important, but distinct roles for p110alpha in the different compartments of the conceptus, which control fetal resource acquisition and growth. |
