Gestational and Lactational Exposure to an Environmentally Relevant Mixture of Brominated Flame Retardants Downregulates Junctional Proteins, Thyroid Hormone Receptor α1 Expression, and the Proliferation-Apoptosis Balance in Mammary Glands Post Puberty
Bibliographic record
Abstract
Mammary gland development requires hormonal regulation during puberty, pregnancy, and lactation. Brominated flame retardants (BFRs) are endocrine disruptors; they are added to consumer products to satisfy flammability standards. Previously, we showed that gestational and lactational exposure to an environmentally relevant mixture of BFRs disrupts proteins of the adherens junctions in rat dam mammary glands at weaning. Here, we hypothesize that perinatal exposure to the same BFR mixture also disrupts junctional proteins and signaling pathways controlling mammary gland development in pups. Dams were exposed through diet to a BFR mixture based on the substances in house dust; doses of the mixture used were 0, 0.06, 20, or 60 mg/kg/day. Dams were exposed continuously beginning prior to mating until pups' weaning; female offspring were euthanized on postnatal day (PND) 21, 46, and 208. The lowest dose of BFRs significantly downregulated adherens junction proteins, E-cadherin, and β-catenin, and the gap junction protein p-Cx43, as well as thyroid hormone receptor alpha 1 protein at PND 46. No effects were observed on estrogen or progesterone receptors. The low dose also resulted in a decrease in cleaved caspase-3, a downward trend in PARP levels, proteins involved in apoptosis, and an upward trend in proliferating cell nuclear antigen, a marker of proliferation. No effects were observed on ductal elongation or on the numbers of terminal end buds. Together, our results indicate that gestational and lactational exposure to an environmentally relevant mixture of BFRs disrupts cell-cell interactions, thyroid hormone homeostasis and the proliferation-apoptosis balance at PND 46, a critical stage for mammary gland development.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot 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.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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 teacher head, 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".