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Record W4253527250 · doi:10.22215/etd/2015-10819

Characterizing the Neurobiological Consequences of Perinatal Exposure to the Obesogenic Endocrine Disruptor Bisphenol-A

2015· dissertation· en· W4253527250 on OpenAlexaff
Harry A. Mackay

Bibliographic record

Venuenot available
Typedissertation
Languageen
FieldEnvironmental Science
TopicEffects and risks of endocrine disrupting chemicals
Canadian institutionsCarleton University
Fundersnot available
KeywordsLeptinEndocrinologyXenoestrogenEndocrine disruptorInternal medicineBenzhydryl compoundsBisphenol AOffspringEndocrine systemAdipose tissueObesityBiologyHormoneChemistryMedicinePregnancyEstrogen receptorCancer

Abstract

fetched live from OpenAlex

Bisphenol-A (BPA) is a component of polycarbonate and many other types of plastics.BPA has been characterized as an endocrine disruptor, most famously due to observations of its estrogenic activity in various experimental models.Because BPA is a common constituent of food and drink containers, and because it can leach out under certain conditions, human exposure is nearly ubiquitous.In this thesis, we demonstrate that CD-1 mice exposed to low, environmentally relevant doses of BPA during the perinatal period exhibit an adult phenotype characterized by sex-specific metabolic disruptions.Specifically, male mice exhibit impaired glucose tolerance, and females a propensity toward diet-induced obesity.Given the sensitivity of the hypothalamus to the organizational effects of sex steroids, we explored the possibility that early-life BPA exposure adversely affects the development of hypothalamic feeding circuitry to bring about these effects.We found that BPA-and diethylstilbestrol (DES)-exposed pups have respectively delayed and blunted postnatal leptin surges-a state of affairs that points to a role for leptin in the organizational effects of early-life xenoestrogen exposure.qRT-PCR analysis of leptin mRNA expression in white adipose tissue collected at the same time suggests that BPA and DES act at the transcriptional level to bring about these effects.Both male and female BPA-exposed mice showed a reduced density of POMC projections into the PVN.This phenotype was rescued in female BPA-exposed animals given daily injections of supplemental leptin (5 µg/g/day).Adult offspring from this experiment were resistant to leptin-induced suppression of food intake, body weight loss, and hypothalamic POMC upregulation.Taken together, these data suggest that BPA, a known obesogen, may exert its effects through developmental programming of the hypothalamic melanocortin circuitry.

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 score0.004

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 integrity0.0000.001
Insufficient payload (model declined to judge)0.0010.000

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 head0.326
Teacher spread0.311 · 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

Citations0
Published2015
Admission routes1
Has abstractyes

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