Evidence map›Paper›PMID 36607602›Full record

ArticleDevelopment (Cambridge, England)2023

The AKT1-FOXO4 axis reciprocally regulates hemochorial placentation.

Keisuke Kozai, Ayelen Moreno-Irusta, Khursheed Iqbal, Mae-Lan Winchester, Regan L Scott, Mikaela E Simon, Masanaga Muto, Marc R Parrish, Michael J Soares

Open access · bronzeAbstract read
In one paragraph

Article in Development (Cambridge, England), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
2.1field-weighted citation impact, top 14% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 7 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 1 institution in 2 countries.

Keisuke KozaiInstitute for Reproductive and Developmental Sciences, Department of Pathology & Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS 66160, USA.ORCID 0000-0003-2645-7431
Ayelen Moreno-IrustaInstitute for Reproductive and Developmental Sciences, Department of Pathology & Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS 66160, USA.ORCID 0000-0001-6810-6475
Khursheed IqbalInstitute for Reproductive and Developmental Sciences, Department of Pathology & Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS 66160, USA.
Mae-Lan WinchesterDepartment of Obstetrics and Gynecology, University of Kansas Medical Center, Kansas City, KS 66160, USA.
Regan L ScottInstitute for Reproductive and Developmental Sciences, Department of Pathology & Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS 66160, USA.ORCID 0000-0001-6294-5294
Mikaela E SimonInstitute for Reproductive and Developmental Sciences, Department of Pathology & Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS 66160, USA.ORCID 0000-0001-5301-2724
Masanaga MutoInstitute for Reproductive and Developmental Sciences, Department of Pathology & Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS 66160, USA.
Marc R ParrishDepartment of Obstetrics and Gynecology, University of Kansas Medical Center, Kansas City, KS 66160, USA.
Michael J SoaresInstitute for Reproductive and Developmental Sciences, Department of Pathology & Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS 66160, USA.ORCID 0000-0001-7158-1592
University of Kansas Medical Center · US

Funding

Mentoring CoreP20GM103418 · NIGMS · UNIVERSITY OF KANSAS MEDICAL CENTER · PI Douglas E Wright · 2012 to 2026
$63.0M
TROPHOBLAST DIFFERENTIATIONR01HD020676 · NICHD · UNIVERSITY OF KANSAS MEDICAL CENTER · PI MICHAEL J SOARES · 1986 to 2026
$10.1M
Stem Cells and Epigenetics of Trophoblast Lineage DevelopmentP01HD079363 · NICHD · UNIVERSITY OF KANSAS MEDICAL CENTER · PI SOARES, MICHAEL J · 2014 to 2018
$5.7M
Anti-Coagulation Factors and PlacentationR01HD099638 · NICHD · UNIVERSITY OF KANSAS MEDICAL CENTER · PI SOARES, MICHAEL J · 2019 to 2023
$2.5M
Trophoblast-Guided Uterine Transformation in the Establishment of PregnancyR01HD105734 · NICHD · UNIVERSITY OF KANSAS MEDICAL CENTER · PI MICHAEL J SOARES · 2022 to 2026
$2.2M
Trophoblast-Uterine Cell Dynamics at the Maternal-Fetal InterfaceR21HD104033 · NICHD · UNIVERSITY OF KANSAS MEDICAL CENTER · PI SOARES, MICHAEL J, TUTEJA, GEETU · 2020 to 2021
$424k
Establishment of the Uterine-Placental InterfaceF31HD104495 · NICHD · UNIVERSITY OF KANSAS MEDICAL CENTER · PI SCOTT, REGAN LEIGH · 2021 to 2025
$169k
Signaling at the Uterine Placental InterfaceF31HD113433 · NICHD · UNIVERSITY OF KANSAS MEDICAL CENTER · PI Mikaela Elizabeth Simon · 2023 to 2026
$152k
NICHD NIH HHS F31 HD104495NICHD NIH HHS F31 HD113433NICHD NIH HHS P01 HD079363NICHD NIH HHS R01 HD020676NICHD NIH HHS R01 HD099638NICHD NIH HHS R01 HD105734NICHD NIH HHS R21 HD104033NIGMS NIH HHS P20 GM103418NIH HHS HD079363NIH HHS HD099638NIH HHS HD104495
6 · The paper itself

Abstract

Hemochorial placentation involves the differentiation of invasive trophoblast cells, specialized cells that possess the capacity to exit the placenta and invade into the uterus where they restructure the vasculature. Invasive trophoblast cells arise from a well-defined compartment within the placenta, referred to as the junctional zone in rat and the extravillous trophoblast cell column in human. In this study, we investigated roles for AKT1, a serine/threonine kinase, in placental development using a genome-edited/loss-of-function rat model. Disruption of AKT1 resulted in placental, fetal and postnatal growth restriction. Forkhead box O4 (Foxo4), which encodes a transcription factor and known AKT substrate, was abundantly expressed in the junctional zone and in invasive trophoblast cells of the rat placentation site. Foxo4 gene disruption using genome editing resulted in placentomegaly, including an enlarged junctional zone. AKT1 and FOXO4 regulate the expression of many of the same transcripts expressed by trophoblast cells, but in opposite directions. In summary, we have identified AKT1 and FOXO4 as part of a regulatory network that reciprocally controls critical indices of hemochorial placenta development.

Indexed as

PlacentaPlacentationAnimalsCell Cycle ProteinsFemaleForkhead Transcription FactorsGene Expression RegulationPregnancyProto-Oncogene Proteins c-aktRatsTrophoblastsUterusAkt1 protein, ratCell Cycle ProteinsForkhead Transcription FactorsFOXO4 protein, ratProto-Oncogene Proteins c-aktAKT1FOXO4Genome editingPlacentaPregnancyRatTrophoblast

Identifiers

PMID36607602
PMCPMC10110493
OpenAlexW4313639855

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.