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Grant support

Centre for Trophoblast Research Next Generation Fellowship Amanda N Sferruzzi-Perri, Royal Society Dorothy Hodgkin Fellowship Amanda N Sferruzzi-Perri, Royal Society Newton International Fellowship Jorge Lopez-Tello, European Cooperation in Science and Technology SALAAM Jorge Lopez-Tello, Erasmus+ Jorge Lopez-Tello, European Cooperation in Science and Technology EPICONCEPT Jorge Lopez-Tello, The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Analysis of institutional authors

Lopez-Tello, JorgeAuthor
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Article

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

Publicated to:eLife. 8 e45282- - 2019-06-26 8(), DOI: 10.7554/eLife.45282

Authors: Lopez-Tello, Jorge; Perez-Garcia, Vicente; Khaira, Jaspreet; Kusinski, Laura C; Cooper, Wendy N; Andreani, Adam; Grant, Imogen; de Liger, Edurne Fernindez; Lam, Brian Y H; Hemberger, Myriam; Sandovici, Ione; Constancia, Miguel; Sferruzzi-Perri, Amanda N

Affiliations

Babraham Inst, Epigenet Programme, Cambridge, England - Author
Rosie Hosp, Dept Obstet & Gynaecol, MRC Metab Dis Unit, Metab Res Labs, Cambridge, England - Author
Univ Calgary, Cumming Sch Med, Dept Biochem & Mol Biol, Calgary, AB, Canada - Author
Univ Calgary, Cumming Sch Med, Dept Med Genet, Calgary, AB, Canada - Author
Univ Cambridge, Ctr Trophoblast Res, Dept Physiol Dev & Neurosci, Cambridge, England - Author
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Abstract

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.

Keywords
1-phosphatidylinositol 3-kinase p110 subunit, mouseAmino-acid-uptakeAnimalsClass i phosphatidylinositol 3-kinasesDevelopmental biologyEmbryonic lethalityEmbryonic stem cellsEnergy metabolismExpressionFemaleFetal developmentFetusGlucose-transportHuman placentaIgf-iiIntrauterine growth restrictionIsoforMiceMicrovillous plasma-membraneMouseNutrient transportPhosphatidylinositol 3-kinasePi3kPlacentaPlacentationPregnancyResource allocationSignal transductionTrophoblasts

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal eLife due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2019, it was in position 5/93, thus managing to position itself as a Q1 (Primer Cuartil), in the category Biology. Notably, the journal is positioned above the 90th percentile.

From a relative perspective, and based on the normalized impact indicator calculated from World Citations provided by WoS (ESI, Clarivate), it yields a value for the citation normalization relative to the expected citation rate of: 1.65. This indicates that, compared to works in the same discipline and in the same year of publication, it ranks as a work cited above average. (source consulted: ESI Nov 14, 2024)

This information is reinforced by other indicators of the same type, which, although dynamic over time and dependent on the set of average global citations at the time of their calculation, consistently position the work at some point among the top 50% most cited in its field:

  • Weighted Average of Normalized Impact by the Scopus agency: 1.12 (source consulted: FECYT Feb 2024)
  • Field Citation Ratio (FCR) from Dimensions: 13.4 (source consulted: Dimensions May 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2025-05-02, the following number of citations:

  • WoS: 27
  • Scopus: 29
  • OpenCitations: 34
Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-05-02:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 18.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 46 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 7.4.
  • The number of mentions on the social network X (formerly Twitter): 12 (Altmetric).

It is essential to present evidence supporting full alignment with institutional principles and guidelines on Open Science and the Conservation and Dissemination of Intellectual Heritage. A clear example of this is:

  • The work has been submitted to a journal whose editorial policy allows open Open Access publication.
Leadership analysis of institutional authors

This work has been carried out with international collaboration, specifically with researchers from: Canada; United Kingdom.

There is a significant leadership presence as some of the institution’s authors appear as the first or last signer, detailed as follows: First Author (LOPEZ TELLO, JORGE) .