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Record W2945616063 · doi:10.1096/fj.201900026r

Uterine Gα <sub>q/11</sub> signaling, in a progesterone‐dependent manner, critically regulates the acquisition of uterine receptivity in the female mouse

2019· article· en· W2945616063 on OpenAlexaff
Vanessa De Oliveira, Jennifer Schaefer, Michele D. Calder, John P. Lydon, Francesco J. DeMayo, Moshmi Bhattacharya, Sally Radovick, Andy V. Babwah

Bibliographic record

VenueThe FASEB Journal · 2019
Typearticle
Languageen
FieldImmunology and Microbiology
TopicReproductive System and Pregnancy
Canadian institutionsWestern University
FundersEunice Kennedy Shriver National Institute of Child Health and Human DevelopmentNational Institutes of HealthNational Institute of Environmental Health SciencesUniversity of Virginia
KeywordsEndocrinologyBiologyInternal medicineSignal transductionUterusReceptorKnockout mouseProgesterone receptorReceptivityCell biologyMyometriumMedicine

Abstract

fetched live from OpenAlex

ABSTRACT A nonreceptive uterus is a major cause of embryo implantation failure. This study examined the importance of the Gα q/11 ‐coupled class of GPCRs as regulators of uterine receptivity. Mice were created lacking uterine Gα q and Gα 11 ; as a result, signaling by all uterine Gα q/11 ‐coupled receptors was disrupted. Reproductive profiling of the knockout females revealed that on d 4 of pregnancy, despite adequate serum progesterone (P4) levels and normal P4 receptor (PR) expression, there was no evidence of PR signaling. This resulted in the down‐regulation of heart and neural crest derivatives expressed 2, Kruppel‐like factor 15, and cyclin G1 and the subsequent persistent proliferation of the luminal epithelium. Aquaporin (Aqp) 11 was also potently down‐regulated, whereas Aηp5 /AQP5 expression persisted, resulting in the inhibition of luminal closure. Hypertrophy of the myometrial longitudinal muscle was also dramatically diminished, likely contributing to the observed implantation failure. Further analyses revealed that a major mechanism via which uterine Gα q/11 signaling induces PR signaling is through the transcriptional up‐regulation of leucine‐rich repeat‐containing GPCR 4 ( Lgr4 ). LGR4 was previously identified as a trigger of PR activation and signaling. Overall, this study establishes that Gα q/11 signaling, in a P4‐dependent manner, critically regulates the acquisition of uterine receptivity in the female mouse, and disruption of such signaling results in P4 resistance.—de Oliveira, V., Schaefer, J., Calder, M., Lydon, J. P., DeMayo, F. J., Bhattacharya, M., Radovick, S., Babwah, A. V. Uterine Gα q/11 signaling, in a progesterone‐dependent manner, critically regulates the acquisition of uterine receptivity in the female mouse. FASEB J. 33, 9374–9387 (2019). www.fasebj.org

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 distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.003
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation 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 score0.039
Threshold uncertainty score0.368

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0030.000
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 science0.0010.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0000.000

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 head0.255
Teacher spread0.241 · 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 teacher head, 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

Citations14
Published2019
Admission routes1
Has abstractyes

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