Dépôt numérique
RECHERCHER

Exposure to an environmentally - relevant dose of Brominated Flame Retardants during pregnancy and lactation reduces β - catenin phosphorylation in a PKA - dependent manner in rat mammary glands

Dianati, Elham; Wade, Mike; Hales, Barbara; Robaire, Bernard; Plante, Isabelle . Exposure to an environmentally - relevant dose of Brominated Flame Retardants during pregnancy and lactation reduces β - catenin phosphorylation in a PKA - dependent manner in rat mammary glands In: 13ème colloque annuelle du centre de recherche Biomed, 28 avril 2017, Cœur des Sciences, UQAM, Montréal (Québec).

Ce document n'est pas hébergé sur EspaceINRS.

Résumé

Mammary gland development requires precise hormonal regulation. We hypothesize that environmental endocrine disruptors may disturb this process. Exposure to one such family of chemicals, the brominated flame retardants (BFR), is ubiquitous. Here, we tested the hypothesis that BFR exposures disrupt signaling pathways that control mammary gland development. Before mating, during pregnancy and throughout lactation, female Sprague - Dawley rats were fed diets containing that BFR mixture based on house dust, delivering nominal exposures of BFR of 0 (control), 0.06, 20 or 60 mg/kg/day. Dams were euthanized and mammary glands collected on postnatal day 21. BFR exposure had no significant effects on mammary gland/body weight ratios or the levels of proteins involved in milk synthesis, epithelial - mesenchymal transition, cell - cell interactions, or hormone signalling. However, BFR exposure (0.06 mg/kg/day) down - regulated phospho - ser675 β - catenin (p - β - cat Ser675 ) levels in the absence of any effect on total β - catenin levels. Levels of p - CREB were also down - regulated, suggesting that PKA inhibition plays a role. p - β - cat Ser675 co - localized with β - catenin at the mammary epithelial cell membrane, and its expression was decreased in animals from the 0.06 and 20 mg/kg/day BFR treatment groups. While β - Catenin signaling was not affected by BFR exposure, the interaction between p - β - cat Ser675 and E - cadherin was significantly reduced. Together, our results demonstrate that exposure to an environmentally relevant mixture of BFR during pregnancy and lactation decreases p - β - cat ser675 at cell adhesion sites, likely in a PKA - dependant manner, altering mammary gland signaling. Further investigation is warranted since dysregulation of β - catenin is associated with abnormal mammary gland development.

Type de document: Document issu d'une conférence ou d'un atelier
Mots-clés libres: -
Centre: Centre INRS-Institut Armand Frappier
Date de dépôt: 26 déc. 2017 17:12
Dernière modification: 26 déc. 2017 17:12
URI: http://espace.inrs.ca/id/eprint/6629

Actions (Identification requise)

Modifier la notice Modifier la notice