In Uteroand Lactational Exposure to an Environmentally Relevant Mixture of Brominated Flame Retardants Induces a Premature Development of the Mammary Glands

Abstract

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 remodelling. 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 α1 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.

Update of the risk assessment of polybrominated diphenyl ethers (PBDEs) in food

“…Several studies were identified in which the experimental animals were exposed to PBDEs together with other BFRs and/or other POPs (Allais et al., 2020 ; Berger et al., 2014 ; Berntsen et al., 2021 ; Dianati et al., 2017 ; Ernest et al., 2012 ; Gouesse et al., 2021 ; Hansen et al., 2019 ; Johanson et al., 2020 ; Khezri et al., 2017 ; Lefevre et al., 2016 ; Mailloux et al., 2014 , 2015 ; Myhre et al., 2021 ; Tung et al., 2016 , 2017 ). The CONTAM Panel did not consider these studies informative for the hazard characterisation of PBDEs and thus these studies were not considered in this Opinion.…”

Environmental, Health, and Legislation Considerations for Rational Design of Nonreactive Flame‐Retardant Additives for Polymeric Materials: Future Perspectives

“…[94] In addition, Gouesse et al recently addressed the premature development of the mammary gland induced from exposure to a mixture of BFRs. [95] Chronic exposure of adult male rats to a mixture HBCDD and BDEs was discussed by Ernest et al and BFR exposure altered thyroid hormone parameters and enlarged kidney and liver but did not affect male reproductive parameters. [96]…”

Design Aspirations for Energy Autarkic Information Systems in a Future with Limits

“…In the printed game instructions there is an elaborate scientific illustration on the operation of solar cells and how they power the game, as well as specific information about the type of lighting and distance required to power it. Unfortunately, over time, the product has yellowed due to the presence of brominated fire retardants, chemicals that leach out of plastics and electronics to disrupt human endocrine development [28]. While a great many other historical consumer devices exist that were designed solar and batteryless during this early period of solar cell manufacture (that continue to work), let us turn now to the design of more contemporary energy autarkic information systems.…”