Evidence map›Paper›PMID 34425190›Full record

ArticleReproductive toxicology (Elmsford, N.Y.)2021

In vitro teratogenicity testing using a 3D, embryo-like gastruloid system.

Veronika Mantziou, Peter Baillie-Benson, Manuela Jaklin, Stefan Kustermann, Alfonso Martínez Arias, Naomi Moris

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Reproductive toxicology (Elmsford, N.Y.), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed, 1 pooled it
–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

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

  1. Pooled it
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  15. Detection of developmental toxicity of the anti-COVID-19 drug molnupiravir using gastruloid-based in vitro assays.Toxicological sciences : an official journal of the Society of Toxicology · 2025
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  20. Three-dimensional stem cell models of mammalian gastrulation.BioEssays : news and reviews in molecular, cellular and developmental biology · 2024
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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

6 authors.

Veronika MantziouDepartment of Genetics, University of Cambridge, Cambridge, UK.
Peter Baillie-BensonDepartment of Genetics, University of Cambridge, Cambridge, UK.
Manuela JaklinF. Hoffmann - La Roche, Pharma Research and Early Development, Roche Innovation Centre Basel, Switzerland; Department for In Vitro Toxicology and Biomedicine Inaugurated by the Doerenkamp-Zbinden Foundation, University of Konstanz, Germany.
Stefan KustermannF. Hoffmann - La Roche, Pharma Research and Early Development, Roche Innovation Centre Basel, Switzerland.
Alfonso Martínez AriasDepartment of Genetics, University of Cambridge, Cambridge, UK.
Naomi MorisDepartment of Genetics, University of Cambridge, Cambridge, UK. Electronic address: naomi.moris@crick.ac.uk.

Funding

Medical Research Council MR/R017190/1Medical Research Council MR/V005367/1
6 · The paper itself

Abstract

Pharmaceuticals intended for use in patients of childbearing potential need to be tested for teratogenicity before marketing. Several pharmaceutical companies use animal-free in vitro models which allow a more rapid selection of lead compounds and contribute to 3Rs principles ('replace, reduce and refine') by streamlining the selection of promising compounds submitted to further regulatory studies in animals. Currently available in vitro models typically rely on adherent monolayer cultures or disorganized 3D structures, both of which lack the spatiotemporal and morphological context of the developing embryo. A newly developed 3D 'gastruloid' model has the potential to achieve a more reliable prediction of teratogenicity by providing a robust recapitulation of gastrulation-like events alongside morphological coordination at relatively high-throughput. In this first proof-of-concept study, we used both mouse and human gastruloids to examine a panel of seven reference compounds, with associated in vivo data and known teratogenic risk, to quantitatively assess in vitro teratogenicity. We observed several gross morphological effects, including significantly reduced elongation or decreased size of the gastruloids, upon exposure to several of the reference compounds. We also observed aberrant gene expression using fluorescent reporters, including SOX2, BRA, and SOX17, suggestive of multi-lineage differentiation defects and disrupted axial patterning. Finally, we saw that gastruloids recapitulated some of the known in vivo species-specific susceptibilities between their mouse and human counterparts. We therefore suggest that gastruloids represent a powerful tool for teratogenicity assessment by enabling relevant physiological recapitulation of early embryonic development, demonstrating their use as a novel in vitro teratogenic model system.

Indexed as

AnimalsCells, CulturedEmbryo, MammalianGastrulaGastrulationHuman Embryonic Stem CellsHumansMiceMouse Embryonic Stem CellsOrganoidsTeratogensTeratogensEmbryonic developmentGastruloidsStem cellsTeratogenicity

Identifiers

PMID34425190
PMCPMC8522962

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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.