Evidence map›Paper›PMID 39255949›Full record

ArticleReproductive toxicology (Elmsford, N.Y.)2024

Examination of piperonyl butoxide developmental toxicity as a Sonic hedgehog pathway inhibitor targeting limb and palate morphogenesis.

Kenneth S Rivera-González, Porsha M Reynolds, Robert J Lipinski

Abstract read
In one paragraph

Article in Reproductive toxicology (Elmsford, N.Y.), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Metabolic stability and effects of microsomal enzymes on the activity of the sonic hedgehog pathway inhibitor piperonyl butoxide.Toxicology in vitro : an international journal published in association with BIBRA · 2026
    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

3 authors.

Kenneth S Rivera-GonzálezDepartment of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI 53706, USA; Molecular and Environmental Toxicology Graduate Training Program, University of Wisconsin-Madison, Madison, WI 53706, USA.
Porsha M ReynoldsDepartment of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI 53706, USA.
Robert J LipinskiDepartment of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI 53706, USA; Molecular and Environmental Toxicology Graduate Training Program, University of Wisconsin-Madison, Madison, WI 53706, USA. Electronic address: robert.lipinski@wisc.edu.

Funding

Molecular & Environmental Toxicology Pre-& Postdoctoral Training ProgramT32ES007015 · NIEHS · UNIVERSITY OF WISCONSIN-MADISON · PI CHRISTOPHER A BRADFIELD · 1985 to 2026
$11.5M
Developmental toxicity of pesticide synergist/Hedgehog inhibitor PBOR01ES026819 · NIEHS · UNIVERSITY OF WISCONSIN-MADISON · PI LIPINSKI, ROBERT · 2018 to 2022
$1.8M
DNA methylation in orofacial cleftingR56DE030917 · NIDCR · UNIVERSITY OF WISCONSIN-MADISON · PI LIPINSKI, ROBERT · 2022 to 2022
$438k
NIDCR NIH HHS R56 DE030917NIEHS NIH HHS R01 ES026819NIEHS NIH HHS T32 ES007015
6 · The paper itself

Abstract

Piperonyl butoxide (PBO) is a pesticide synergist with widespread use and human exposure that was discovered to inhibit Sonic hedgehog (Shh) signaling, a pathway required for numerous developmental processes. Previous examinations of PBO's potential for developmental toxicity have generated seemingly conflicting results. We investigated the impact of acute PBO exposure targeting Shh pathway activity during palate and limb morphogenesis. Timed-pregnant C57BL/6 J mice were exposed to a single PBO dose (67-1800 mg/kg) at gestational day (GD) 9.75, and litters were collected at GD10.25 and GD10.75 to examine Shh pathway activity or GD17 for phenotypic assessment. PBO exposure induced dose-dependent limb malformations and cleft palate in the highest dose group. Following PBO exposure, reduced expression of the Shh pathway activity markers Gli1 and Ptch1 was observed in the embryonic limb buds and craniofacial processes. These findings provide additional evidence that prenatal PBO exposure targeting Shh pathway activity can result in malformations in mice that parallel common etiologically complex human birth defects.

Indexed as

Hedgehog ProteinsMice, Inbred C57BLMorphogenesisPiperonyl ButoxideSignal TransductionAnimalsCleft PalateExtremitiesFemaleMicePalatePatched-1 ReceptorPregnancyZinc Finger Protein GLI1Gli1 protein, mouseHedgehog ProteinsPatched-1 ReceptorPiperonyl ButoxidePtch1 protein, mouseShh protein, mouseZinc Finger Protein GLI1Cleft palateLimb malformationsPesticidesPiperonyl butoxide (PBO)Sonic hedgehog (Shh)

Identifiers

PMID39255949
PMCPMC11624992

What OpenQuestion holds

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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.