Evidence map›Paper›PMID 34556114›Full record

ArticleBMC biology2021

Self-organising human gonads generated by a Matrigel-based gradient system.

Elizabeth Oliver, João Pedro Alves-Lopes, Femke Harteveld, Rod T Mitchell, Elisabet Åkesson, Olle Söder, Jan-Bernd Stukenborg

Open access · goldAbstract read
In one paragraph

Article in BMC biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed, 1 pooled it
4.8field-weighted citation impact, top 5% 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

26 citing papers in PubMed, 1 synthesis or guideline pooled it, 40 citations in OpenAlex.

  1. Pooled it
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  7. In vitro models of the male reproductive system: applications for developmental and reproductive toxicology.Toxicological sciences : an official journal of the Society of Toxicology · 2025
    Review
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  14. A new humanHuman reproduction open · 2025
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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

7 authors at 3 institutions in 2 countries.

Elizabeth Oliver *NORDFERTIL Research Lab Stockholm, Childhood Cancer Research Unit, J9:30, Department of Women's and Children's Health, Karolinska Institutet and Karolinska University Hospital, Visionsgatan 4, 17164, Solna, Stockholm, Sweden.
João Pedro Alves-Lopes *NORDFERTIL Research Lab Stockholm, Childhood Cancer Research Unit, J9:30, Department of Women's and Children's Health, Karolinska Institutet and Karolinska University Hospital, Visionsgatan 4, 17164, Solna, Stockholm, Sweden.
Femke HarteveldNORDFERTIL Research Lab Stockholm, Childhood Cancer Research Unit, J9:30, Department of Women's and Children's Health, Karolinska Institutet and Karolinska University Hospital, Visionsgatan 4, 17164, Solna, Stockholm, Sweden.
Rod T MitchellMRC Centre for Reproductive Health, The Queen's Medical Research Institute, The University of Edinburgh, 47 Little France Crescent, Edinburgh, Scotland, EH16 4TJ, UK.
Elisabet ÅkessonDepartment of Neurobiology, Care Sciences & Society, Division of Neurogeriatrics, Karolinska Institutet, Stockholm, Sweden.
Olle SöderNORDFERTIL Research Lab Stockholm, Childhood Cancer Research Unit, J9:30, Department of Women's and Children's Health, Karolinska Institutet and Karolinska University Hospital, Visionsgatan 4, 17164, Solna, Stockholm, Sweden.
Jan-Bernd StukenborgNORDFERTIL Research Lab Stockholm, Childhood Cancer Research Unit, J9:30, Department of Women's and Children's Health, Karolinska Institutet and Karolinska University Hospital, Visionsgatan 4, 17164, Solna, Stockholm, Sweden. jan-bernd.stukenborg@ki.se.ORCID 0000-0002-2839-1870
Karolinska University Hospital · SEKarolinska Institutet · SERoyal Hospital for Children · GB

Funding

Medical Research Council MR/S017151/1
6 · The paper itself

Abstract

backgroundAdvances in three-dimensional culture technologies have led to progression in systems used to model the gonadal microenvironment in vitro. Despite demonstrating basic functionality, tissue organisation is often limited. We have previously detailed a three-dimensional culture model termed the three-layer gradient system to generate rat testicular organoids in vitro. Here we extend the model to human first-trimester embryonic gonadal tissue.

resultsTesticular cell suspensions reorganised into testis-like organoids with distinct seminiferous-like cords situated within an interstitial environment after 7 days. In contrast, tissue reorganisation failed to occur when mesonephros, which promotes testicular development in vivo, was included in the tissue digest. Organoids generated from dissociated female gonad cell suspensions formed loosely organised cords after 7 days. In addition to displaying testis-specific architecture, testis-like organoids demonstrated evidence of somatic cell differentiation. Within the 3-LGS, we observed the onset of AMH expression in the cytoplasm of SOX9-positive Sertoli cells within reorganised testicular cords. Leydig cell differentiation and onset of steroidogenic capacity was also revealed in the 3-LGS through the expression of key steroidogenic enzymes StAR and CYP17A1 within the interstitial compartment. While the 3-LGS generates a somatic cell environment capable of supporting germ cell survival in ovarian organoids germ cell loss was observed in testicular organoids.

conclusionThe 3-LGS can be used to generate organised whole gonadal organoids within 7 days. The 3-LGS brings a new opportunity to explore gonadal organogenesis and contributes to the development of more complex in vitro models in the field of developmental and regenerative medicine.

Indexed as

Sertoli CellsTestisAnimalsCollagenDrug CombinationsFemaleGonadsHumansLamininMaleProteoglycansRatsSuspensionsCollagenDrug CombinationsLamininmatrigelProteoglycansSuspensionsDevelopmentGerm cellsLeydig cellsOrganoidsOvarySertoli cellsTestis

Identifiers

PMID34556114
PMCPMC8461962
OpenAlexW3200012070

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.