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Record W3194397255 · doi:10.1038/s41593-021-00896-4

Placental endocrine function shapes cerebellar development and social behavior

2021· article· en· W3194397255 on OpenAlexaff
Claire‐Marie Vacher, Hélène Lacaille, Jiaqi J. O’Reilly, Jacquelyn Salzbank, Dana Bakalar, Sonia Sebaoui, Philippe Lière, Cheryl Clarkson‐Paredes, Toru Sasaki, A. G. Sathyanesan, Panagiotis Kratimenos, Jacob Ellegood, Jason P. Lerch, Yuka Imamura Kawasawa, Anastas Popratiloff, Kazue Hashimoto‐Torii, Vittorio Gallo, Michaël Schumacher, Anna A. Penn

Bibliographic record

VenueNature Neuroscience · 2021
Typearticle
Languageen
FieldMedicine
TopicNeonatal and fetal brain pathology
Canadian institutionsHospital for Sick Children
FundersNational Institute of Neurological Disorders and StrokeIntellectual and Developmental Disabilities Research CenterNational Institutes of HealthCerebral Palsy AllianceEunice Kennedy Shriver National Institute of Child Health and Human DevelopmentAgence Nationale de la RechercheSimons Foundation Autism Research InitiativeChildren's National HospitalCerebral Palsy Alliance Research FoundationSimons Foundation
KeywordsNeuroscienceCerebellumEndocrine systemFunction (biology)PsychologyBiologyEndocrinologyCell biologyHormone

Abstract

fetched live from OpenAlex

Abstract Compromised placental function or premature loss has been linked to diverse neurodevelopmental disorders. Here we show that placenta allopregnanolone (ALLO), a progesterone-derived GABA-A receptor (GABA A R) modulator, reduction alters neurodevelopment in a sex-linked manner. A new conditional mouse model, in which the gene encoding ALLO’s synthetic enzyme ( akr1c14 ) is specifically deleted in trophoblasts, directly demonstrated that placental ALLO insufficiency led to cerebellar white matter abnormalities that correlated with autistic-like behavior only in male offspring. A single injection of ALLO or muscimol, a GABA A R agonist, during late gestation abolished these alterations. Comparison of male and female human preterm infant cerebellum also showed sex-linked myelination marker alteration, suggesting similarities between mouse placental ALLO insufficiency and human preterm brain development. This study reveals a new role for a placental hormone in shaping brain regions and behaviors in a sex-linked manner. Placental hormone replacement might offer novel therapeutic opportunities to prevent later neurobehavioral disorders.

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: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.002
Threshold uncertainty score0.006

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0020.000

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 head0.015
GPT teacher head0.271
Teacher spread0.256 · 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 designObservational
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

Citations116
Published2021
Admission routes1
Has abstractyes

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