Exposure to Brominated Flame Retardants During Pregnancy and Lactation Increases the Prevalence of Breast Lesions and Cancer-Associated Pathways in Sprague-Dawley Rats

McDermott, Alec; Juarez Velazquez, Melany; Wade, Michael G.; Patten, Shunmoogum A. ORCID: https://orcid.org/0000-0002-2782-3547 et Plante, Isabelle ORCID: https://orcid.org/0000-0003-2080-6450 (2025). Exposure to Brominated Flame Retardants During Pregnancy and Lactation Increases the Prevalence of Breast Lesions and Cancer-Associated Pathways in Sprague-Dawley Rats Reproductive Toxicology , vol. 135 , nº 108928. pp. 1-14. DOI: 10.1016/j.reprotox.2025.108928.

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Résumé

The mammary gland undergoes significant changes during pregnancy, lactation, and involution, making it highly susceptible to endocrine-disrupting chemicals such as brominated flame retardants (BFRs). Despite being restricted in many countries, some BFRs persist in the environment and accumulate in human tissues, including the mammary gland and human milk. This study investigates the effects of BFRs exposure during pregnancy and lactation on mammary gland development and breast cancer risk in a rat model. Dams were exposed to a mixture of polybrominated diphenyl ethers (PBDEs) and hexabromocyclododecane (HBCDD), formulated based on relative congener levels found in house dust. Post-weaning, dams were treated with 7,12-dimethylbenz[a]anthracene (DMBA) to initiate tumor formation. The results revealed that both low and high doses of BFRs induced lesions in mammary epithelium, with an increase in total lesion number in low dose. Molecular analysis revealed disruptions in the Wnt/β-catenin signaling pathway, leading to an increase in oncogene expression, including c-Myc and c-Jun. RNA sequencing also indicated dysregulation in calcium signaling and glucose metabolism pathways. Our findings suggest that BFR exposure during the critical window of mammary gland involution compromises the cancer-protective effects of pregnancy and lactation. These effects are particularly significant at low exposure levels, demonstrating a non-monotonic dose-response. The study underscores the potential long-term health risks associated with environmental BFR exposure and highlights the need for further research on its implications on the risks of developing breast cancer later in life.

Type de document:	Article
Informations complémentaires:	This study was supported by a grant from the Cancer Research Society (#24081) to IP and MW. AM was the recipient of IRSC and FRQS scholarships. MJ was the recipient of the Armand-Frappier Foundation scholarship
Mots-clés libres:	Mammary gland development; Breast cancer risks; Brominated flame retardants; Wnt/β-catenin signaling; Endocrine-disrupting chemicals
Centre:	Centre INRS-Institut Armand Frappier
Date de dépôt:	07 juill. 2025 18:52
Dernière modification:	07 juill. 2025 18:52
URI:	https://espace.inrs.ca/id/eprint/16491

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