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Record W4409907021 · doi:10.1016/j.taap.2025.117355

Mouse nephron formation is impaired by moderate dose arsenical exposure

2025· article· en· W4409907021 on OpenAlexafffund
Carlos Agustín Isidro Alonso, Jenna Haverfield, Gabriela Regalado, Sihem Sellami, Natascha Gagnon, Ajay Rajaram, Pierre Fiset, Tomoko Takano, Aimee K. Ryan, Koren K. Mann, Indra R. Gupta

Bibliographic record

VenueToxicology and Applied Pharmacology · 2025
Typearticle
Languageen
FieldEnvironmental Science
TopicArsenic contamination and mitigation
Canadian institutionsMcGill UniversityJewish General HospitalMcGill University Health Centre
FundersFondation de l'Hôpital de Montréal pour enfants
KeywordsNephronKidney developmentKidneyUreteric budOffspringInternal medicineEndocrinologyIn uteroBiologyTeratologyMesenchymeGestationEmbryonic stem cellEmbryoFetusPregnancyCell biologyMedicineBiochemistry

Abstract

fetched live from OpenAlex

Millions of people are exposed to concentrations of arsenic that exceed the World Health Organization's limit of 10 μg/L. Inorganic arsenic (iAsIII) is metabolized by arsenic 3 methyltransferase (As3mt) that converts it to methylated arsenicals, mono and dimethyl arsonous acid (MMA and DMA). Chronic arsenic exposure is linked to an increased risk of chronic kidney disease (CKD), however, the effects of arsenic exposure on kidney development remain unclear. We hypothesized that exposure to arsenicals impairs nephron formation during mouse kidney development. Mouse embryonic kidney explants were treated with iAsIII and MMAIII (1.5 μM or 200 μg/L). iAsIII inhibited growth of kidney explants and ureteric bud branching morphogenesis at embryonic day 11.5 (E11.5) and E12.5, but not at E13.5. Similar effects were observed when kidney explants were treated with MMAIII. Additionally, iAsIII exposure increased apoptosis in the metanephric mesenchyme of E11.5 explants and decreased Gdnf transcription. To assess the impact of iAS exposure in utero and early postnatal life, female mice harboring a humanized version of AS3MT and wild-type mice with murine As3mt were exposed to iAsIII throughout gestation and weaning and their offspring were analyzed for kidney defects. Pups with human AS3MT exposed to 1.5 μM iAsIII in utero, showed a 20 % reduction in kidney weight normalized to body weight and a 28 % reduction in nephron number, compared to kidneys of wild-type mice. In conclusion, exposure to arsenicals during embryonic development impairs ureteric bud branching morphogenesis and decreases nephron endowment, which may predispose to CKD in adulthood.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.004
Threshold uncertainty score0.014

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0020.000
Science and technology studies0.0000.001
Scholarly communication0.0010.000
Open science0.0010.001
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0040.001

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.008
GPT teacher head0.259
Teacher spread0.251 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations2
Published2025
Admission routes2
Has abstractyes

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