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Record W4401384599 · doi:10.1038/s41467-024-48897-8

Male autism spectrum disorder is linked to brain aromatase disruption by prenatal BPA in multimodal investigations and 10HDA ameliorates the related mouse phenotype

2024· article· en· W4401384599 on OpenAlexafffund
Christos Symeonides, Kristina Vacy, Sarah Thomson, Samuel Tanner, H. Chua, Shilpi Dixit, Toby Mansell, Martin O’Hely, Boris Novakovic, Julie B. Herbstman, Shuang Wang, Jia Guo, Jessalynn Chia, Nhi T. Tran, S. Hwang, Kara L. Britt, Tae Hwan Kim, Christopher A. Reid, Anthony El-Bitar, Gabriel B. Bernasochi, Lea M.D. Delbridge, Vincent R. Harley, Yann Wan Yap, Deborah Dewey, Chloe J. Love, David Burgner, Mimi L.K. Tang, Peter D. Sly, Richard Saffery, Jochen F. Mueller, Nicole Rinehart, Bruce J. Tonge, Peter Vuillermin

Bibliographic record

VenueNature Communications · 2024
Typearticle
Languageen
FieldEnvironmental Science
TopicEffects and risks of endocrine disrupting chemicals
Canadian institutionsUniversity of Calgary
FundersNational Health and Medical Research CouncilCanadian Institutes of Health ResearchBarwon Health FoundationArmstrong FoundationPercy Baxter Charitable TrustState Government of VictoriaEuropean CommissionShepherd FoundationMinderoo FoundationDeakin UniversityMurdoch Children's Research InstituteMedical Research CouncilChildren’s Hospital of Wisconsin Research Institute
KeywordsAromataseAutismInternal medicineAutism spectrum disorderEndocrinologyMethylationNeurodevelopmental disorderPregnancyDNA methylationMedicineBiologyGene expressionGeneGeneticsPsychiatry

Abstract

fetched live from OpenAlex

Male sex, early life chemical exposure and the brain aromatase enzyme have been implicated in autism spectrum disorder (ASD). In the Barwon Infant Study birth cohort (n = 1074), higher prenatal maternal bisphenol A (BPA) levels are associated with higher ASD symptoms at age 2 and diagnosis at age 9 only in males with low aromatase genetic pathway activity scores. Higher prenatal BPA levels are predictive of higher cord blood methylation across the CYP19A1 brain promoter I.f region (P = 0.009) and aromatase gene methylation mediates (P = 0.01) the link between higher prenatal BPA and brain-derived neurotrophic factor methylation, with independent cohort replication. BPA suppressed aromatase expression in vitro and in vivo. Male mice exposed to mid-gestation BPA or with aromatase knockout have ASD-like behaviors with structural and functional brain changes. 10-hydroxy-2-decenoic acid (10HDA), an estrogenic fatty acid alleviated these features and reversed detrimental neurodevelopmental gene expression. Here we demonstrate that prenatal BPA exposure is associated with impaired brain aromatase function and ASD-related behaviors and brain abnormalities in males that may be reversible through postnatal 10HDA intervention.

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 score0.005
Threshold uncertainty score0.018

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0050.000

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 head0.007
GPT teacher head0.313
Teacher spread0.307 · 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

Citations55
Published2024
Admission routes2
Has abstractyes

Explore more

Same venueNature CommunicationsSame topicEffects and risks of endocrine disrupting chemicalsFrench-language works237,207