Dataset Information

Gestational and Lactational Exposure to an Environmentally-relevant Mixture of Brominated Flame Retardants Down-regulates Junctional Proteins, Thyroid Hormone Receptor ?1 Expression and the Proliferation-Apoptosis Balance in Mammary Glands Post Puberty.

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 down-regulated adherens junction proteins, E-cadherin and ?-catenin, and the gap junction protein p-Cx43, as well as thyroid hormone receptor alpha1 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 PCNA, 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.

SUBMITTER: Gouesse RJ

PROVIDER: S-EPMC6735962 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Publications

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.

Gouesse Rita-Josiane RJ Lavoie Mélanie M Dianati Elham E Wade Mike G MG Hales Barbara F BF Robaire Bernard B Plante Isabelle I

Toxicological sciences : an official journal of the Society of Toxicology 20190901 1

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 disr ...[more]

PMID: 31241157

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Project description:Brominated flame retardants (BFRs) are now ubiquitous contaminants with large reservoirs and high concentrations in buildings. Most of the information documenting BFR levels has been obtained in residences, and other environments that can lead to exposure have received relatively little attention, including offices that contain numerous BFR sources and where individuals spend considerable time. The aim of this study is to characterize BFR concentrations, potential emission sources, and migration pathways in office environments. We measure BFR levels in floor dust, indoor air, ventilation filter dust, and carpets in ten commercial and institutional buildings in Michigan, U.S.A. The median concentration of total BDEs in settled dust was 8754 ng g(-1), at the upper range of levels previously reported. Especially elevated levels were found in offices in buildings that contained known or likely BFR sources, e.g., computer servers. A trends analysis in a newly constructed building showed remarkable increases in concentrations of BFRs in settled dust and indoor air, and apparent steady-state levels were reached 5 to 8 months after building completion, a particularly striking finding given that the building was constructed and furnished several years after the voluntary phase-out of the penta- and octa-mixtures. Airborne particulate matter collected in a building's HVAC system filters contained PBDEs, including BDE-209, at levels exceeding the concentration of floor dust. In conjunction with estimates of building air flow rates, filter efficiency and other parameters, mass balance calculations for this building were used to estimate the emission rates and reservoirs of PBDEs. The widespread distribution of BFRs found in offices in both new and old buildings suggests the significance of workplace exposures, the need for controls to minimize human exposure, intra-building migration, and environmental releases of these chemicals, and the need for monitoring in new buildings to confirm the effectiveness of the PBDE phase-out.

Dataset Information

Gestational and Lactational Exposure to an Environmentally-relevant Mixture of Brominated Flame Retardants Down-regulates Junctional Proteins, Thyroid Hormone Receptor ?1 Expression and the Proliferation-Apoptosis Balance in Mammary Glands Post Puberty.

Publications

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.

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