Journal
TOXICOLOGICAL SCIENCES
Volume 179, Issue 2, Pages 206-219Publisher
OXFORD UNIV PRESS
DOI: 10.1093/toxsci/kfaa176
Keywords
endocrine disruptors; brominated flame retardants; in utero and lactational exposure; mammary gland; precocious development; low-dose effects; proliferation; apoptosis; thyroid hormone receptor
Categories
Funding
- Natural Sciences and Engineering Research Council of Canada [RGPIN-2020-05726]
- Canadian Institutes of Health Research
- Institute of Human Development, Child and Youth Health [RHF100625]
- Chemicals Management Research Initiative Fund of Health Canada
- Ministere de l'Enseignement Superieur et de la Recherche Scientifique de Cote d'Ivoire
- Reseau Quebecois en reproduction-CIRD
- Fondation Armand-Frappier scholarships
Ask authors/readers for more resources
Exposure to environmentally relevant mixture of BFRs induces precocious development of the mammary gland in young animals, accelerating epithelial development, increasing cell proliferation and apoptosis, as well as the number of thyroid hormone receptor alpha 1 positive cells.
In utero and prepubertal development of the mammary glands occurs minimally in a hormone independent manner until puberty where maturation of the hypothalamic-pituitary-gonadal axis drives an extensive remodeling. Nevertheless, because the immature glands contain functional hormone receptors, they are especially vulnerable to the effects of endocrine disruptors, such as brominated flame retardants (BFRs). BFRs are widespread chemicals added to household objects to reduce their flammability, and to which humans are ubiquitously exposed. We previously reported that in utero and lactational exposure to BFRs resulted in an impaired mammary gland development in peripubertal animals. Here, we assessed whether BFR-induced disruption of mammary gland development could manifest earlier in life. Dams were exposed prior to mating until pups' weaning to a BFR mixture (0, 0.06, 20, or 60 mg/kg/day) formulated according to levels found in house dust. The mammary glands of female offspring were collected at weaning. Histo-morphological analyses showed that exposure to 0.06 mg/kg/day accelerates global epithelial development as demonstrated by a significant increase in total epithelial surface area, associated with a tendency to increase of the ductal area and thickness, and of lumen area. Significant increases of the Ki67 cell proliferation index and of the early apoptotic marker cleaved caspase-9 were also observed, as well as an upward trend in the number of thyroid hormone receptor alpha 1 positive cells. These molecular, histologic, and morphometric changes are suggestive of accelerated pubertal development. Thus, our results suggest that exposure to an environmentally relevant mixture of BFRs induces precocious development of the mammary gland.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available