Evidence map›Paper›PMID 40605617›Full record

ArticleEndocrinology2025

NEDD4 Promotes Sertoli Cell Proliferation and Adult Leydig Cell Differentiation in the Murine Testis.

Simon Peter Windley, Yasmine Neirijnck, Diana Vidovic, Quenten Schwarz, Sharad Kumar, Serge Nef, Dagmar Wilhelm

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Endocrinology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. Article
  2. Article
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

7 authors.

Simon Peter WindleyDepartment of Anatomy & Physiology, The University of Melbourne, Parkville 3100, Australia.ORCID 0000-0002-8718-1558
Yasmine NeirijnckDepartment of Genetics, Medicine & Development, University of Geneva, 1211 Geneva, Switzerland.ORCID 0000-0001-7236-8451
Diana VidovicDepartment of Anatomy & Physiology, The University of Melbourne, Parkville 3100, Australia.ORCID 0000-0002-9460-4926
Quenten SchwarzCentre for Cancer Biology, University of South Australia and SA Pathology, Adelaide 5001, Australia.ORCID 0000-0002-5958-4181
Sharad KumarCentre for Cancer Biology, University of South Australia and SA Pathology, Adelaide 5001, Australia.ORCID 0000-0001-7126-9814
Serge NefDepartment of Genetics, Medicine & Development, University of Geneva, 1211 Geneva, Switzerland.ORCID 0000-0001-5462-0676
Dagmar WilhelmDepartment of Anatomy & Physiology, The University of Melbourne, Parkville 3100, Australia.ORCID 0000-0002-7757-4075

Funding

Australian Research Council 150101448Monash University Biomedicine Discovery InstituteNational Health and Medical Research Council of Australia GNT 2007739Swiss National Science Foundation 310030_200316Swiss National Science Foundation 31003A_173070
6 · The paper itself

Abstract

Successful testis development relies on the coordinated differentiation and assembly of various cell types to establish both endocrine and reproductive functions. The ubiquitin ligase NEDD4 has emerged as a key player in murine testis development, with this enzyme being implicated in gonadal sex determination and spermatogonial stem cell differentiation. Here, we report hitherto uncharacterized roles of NEDD4 in postnatal testis development. Utilizing Nr5a1- and Amh-Cre drivers to conditionally ablate Nedd4 in testicular somatic cells, we show that NEDD4 promotes Sertoli cell proliferation through the modulation of the PI3K-AKT signaling pathway. This ubiquitin ligase also ensures proper differentiation of adult Leydig cells and may contribute to murine steroidogenesis. Furthermore, NEDD4 is essential for adrenal gland differentiation, as its loss results in adrenal dysgenesis. These findings highlight NEDD4 as a crucial factor in testis development, emphasizing the importance of ubiquitination and post-translational modifications in reproductive biology.

Indexed as

Cell DifferentiationCell ProliferationEndosomal Sorting Complexes Required for TransportLeydig CellsNedd4 Ubiquitin Protein LigasesSertoli CellsTestisUbiquitin-Protein LigasesAnimalsMaleMicePhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktSignal TransductionUbiquitinationEndosomal Sorting Complexes Required for TransportNedd4 protein, mouseNedd4 Ubiquitin Protein LigasesPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktUbiquitin-Protein Ligasesadrenal dysgenesisNEDD4steroidogenesistestis developmenttestis function

Identifiers

PMID40605617
PMCPMC12280327

What OpenQuestion holds

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Registered trials

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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.