Perinatal Exposure to Low-Dose Bisphenol-A Disrupts the Structural and Functional Development of the Hypothalamic Feeding Circuitry
Bibliographic record
Abstract
Bisphenol-A (BPA) is a component of polycarbonate and other plastics to which humans are regularly exposed at low levels. BPA is characterized as an endocrine disruptor because of observations of its estrogenic activity in various experimental models. We have previously shown evidence of disrupted hypothalamic feeding circuitry and leptin sensitivity in adult BPA-exposed animals subjected to a high-fat diet, but because these animals were already exhibiting a diet-induced obese phenotype, we could not rule out the possibility that these observations were simply consequences of the obesity, not a preexisting phenotype produced by BPA exposure. Here, we studied leptin sensitivity and hypothalamic structure in young BPA-exposed animals before the onset of a body weight or metabolic phenotype. Pregnant and lactating CD-1 mice were exposed to either BPA or diethylstilbestrol (DES) at low, environmentally relevant doses via their diet. Studies of leptin function and neurobiology were conducted on offspring at several time points. Young adult offspring from this experiment were resistant to leptin-induced suppression of food intake, body weight loss, and hypothalamic pro-opiomelanocortin (POMC) upregulation. Both male and female BPA-exposed mice showed a reduced density of POMC projections into the paraventricular nucleus of the hypothalamus (PVN). BPA- and DES-exposed pups had respectively delayed and blunted postnatal leptin surges, and POMC projections into the PVN were rescued in female BPA-exposed animals given daily injections of supplemental leptin. Our findings suggest that BPA, a putative obesogen, may exert its effects through developmental programming of the hypothalamic melanocortin circuitry, permanently altering the neurobiology of metabolic homeostasis.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot 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.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
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".