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Evaluating the effect of chronic exposure of Brominated Flame Retardants on lactating mammary glands of female rats

Dianati, Elham; Wade, Mike; Hales, Barbara; Plante, Isabelle . Evaluating the effect of chronic exposure of Brominated Flame Retardants on lactating mammary glands of female rats In: 12ème colloque du centre de recherche Biomed, 5 mai 2016, Centre de congrès Palace, Laval (Québec).

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Résumé

Brominated flame retardants (BFRs) are a major class of compounds added to many consumers products to reduce fire hazard and ignition rates. BFRs are abundantly used in textiles, foams, plastics, furniture and home electronics. Researches have shown that these chemicals leach out in to our environments prompting human chronic exposure throughout inhalation and ingestion. Moreover, BFRs are lipophilic and can accumulate in serum, milk as well as adipose tissues such as mammary glands. Even though BFRs usage has been restricted for more than 10 years, their levels in house dust as well as human body fluid remained fairly constant. BFRs have been also reported to be endocrine disruptors through estrogen and thyroxin activities. Normal development and function of the mammary gland including ductal development, alveologenesis and milk secretion require synergy of different hormones and cell - cell interactions during puberty, pregnancy and lactation. Thereby endocrine disruptors can perturb this normal physiology and dysregulate cell - cell communications. Our main objective was to evaluate whether exposure to BFRs during alveologenesis and lactation can affect mammary glands normal physiology and function. Female Sprague Dawley rats (N≥9) were randomly assigned to four different groups (control (vehicle), low (0.06 mg/kg/BW), medium (20 mg/kg/BW) and high (60 mg/kg/BW)) which were exposed to different doses of mixed BFRs congeners through diets starting two weeks prior to the mating, during pregnancy and throughout lactation. Females were sacrificed on the day of weaning and mammary glands were excised. Our results showed that BFRs had no significant effect on total body weight or mammary gland Weight. Milk synthesis and secretion were not affected by the BFRs treatments, as there were no differences in pups’ growth, or in protein levels of Stat5, phospho - Stat5 and β - casein protein levels. Similarly, BFRs treatment did not affect EGFR, phospho - EGFR or ER α, receptors which are important for mammary gland normal development and function. E - cadherin, N - cadherin and Vimentin, as well as P - cadherin, Claudin - 7, Occludin, Connexin43, Connexin32, markers of the epithelial - to - mesenchymal transition and of cell - cell interactions respectively, were not affected either. Interestingly, while β - catenin levels were not affected by the treatment, our re- sults showed a significant down - regulation in phospho - β - catenin protein level in animals treated with the medium dose. Analysis of Gsk3 β and phospho - Gsk3 β, which are known to be part of wnt/ β catenin canonical pathway by phosphorylating β - catenin and targeting it for down - regulation, confirmed that β - catenin down - regulation does not occur through the function of this kinase. Further analysis is required to reveal the mechanisms underlying and the signaling pathways involved. Together, our results showed that an exposure to BFRs have moderate effects on pregnancy - related mammary gland development. Financed by NSERC and FRQS (IP), by FUAFI (ED), CIHR (ML, BH, MW) and Health Canada CMP (MW).

Type de document: Document issu d'une conférence ou d'un atelier
Informations complémentaires: Présentation par affiche
Mots-clés libres: -
Centre: Centre INRS-Institut Armand Frappier
Date de dépôt: 26 déc. 2017 17:01
Dernière modification: 26 déc. 2017 17:01
URI: http://espace.inrs.ca/id/eprint/6628

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