Evidence map›Paper›PMID 34403436›Full record

ArticlePloS one2021

Developmental malformations resulting from high-dose maternal tamoxifen exposure in the mouse.

Miranda R Sun, Austin C Steward, Emma A Sweet, Alexander A Martin, Robert J Lipinski

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed, 1 pooled it
2.6field-weighted citation impact, top 10% 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

17 citing papers in PubMed, 1 synthesis or guideline pooled it, 22 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. A new conditional mouse model for Cre-mediated restoration ofbioRxiv : the preprint server for biology · 2026
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  7. Characterization of theFASEB bioAdvances · 2025
    Article
  8. Article
  9. Review
  10. Disruption of DNA methylation-mediated cranial neural crest proliferation and differentiation causes orofacial clefts in mice.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  11. Article
  12. The duct of von Ebner's glands is a source ofFrontiers in cell and developmental biology · 2024
    Article
  13. Article
  14. Review
  15. Article
  16. Limitations of Tamoxifen Application for In Vivo Genome Editing Using Cre/ERInternational journal of molecular sciences · 2022
    Article
  17. 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

5 authors at 1 institution in 1 country.

Miranda R SunDepartment of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI, United States of America.
Austin C StewardDepartment of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI, United States of America.
Emma A SweetDepartment of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI, United States of America.
Alexander A MartinDepartment of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI, United States of America.
Robert J LipinskiDepartment of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI, United States of America.ORCID 0000-0002-1994-4090
University of Wisconsin–Madison · US

Funding

Short-Term Research Training of Veterinary Students in WisconsinT35OD011078 · OD · UNIVERSITY OF WISCONSIN-MADISON · PI BJORLING, DALE EDMOND, JORGENSEN, JOAN S · 2012 to 2025
$1.0M
NIH HHS T35 OD011078
6 · The paper itself

Abstract

Tamoxifen is an estrogen receptor (ER) ligand with widespread use in clinical and basic research settings. Beyond its application in treating ER-positive cancer, tamoxifen has been co-opted into a powerful approach for temporal-specific genetic alteration. The use of tamoxifen-inducible Cre-recombinase mouse models to examine genetic, molecular, and cellular mechanisms of development and disease is now prevalent in biomedical research. Understanding off-target effects of tamoxifen will inform its use in both clinical and basic research applications. Here, we show that prenatal tamoxifen exposure can cause structural birth defects in the mouse. Administration of a single 200 mg/kg tamoxifen dose to pregnant wildtype C57BL/6J mice at gestational day 9.75 caused cleft palate and limb malformations in the fetuses, including posterior digit duplication, reduction, or fusion. These malformations were highly penetrant and consistent across independent chemical manufacturers. As opposed to 200 mg/kg, a single dose of 50 mg/kg tamoxifen at the same developmental stage did not result in overt structural malformations. Demonstrating that prenatal tamoxifen exposure at a specific time point causes dose-dependent developmental abnormalities, these findings argue for more considerate application of tamoxifen in Cre-inducible systems and further investigation of tamoxifen's mechanisms of action.

Indexed as

AnimalsCleft PalateDose-Response Relationship, DrugFemaleFetusGene ExpressionHumansIntegrasesLimb Deformities, CongenitalMaternal ExposureMiceMice, Inbred C57BLMice, TransgenicPregnancyPrenatal Exposure Delayed EffectsSelective Estrogen Receptor ModulatorsCre recombinaseIntegrasesSelective Estrogen Receptor ModulatorsTamoxifenTeratogens

Identifiers

PMID34403436
PMCPMC8370643
OpenAlexW3195770009

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.