Best practices to quantify the impact of reproductive toxicants on development, function, and diseases of the rodent mammary gland

Work from numerous fields of study suggests that exposures to hormonally active chemicals during sensitive windows of development can alter mammary gland development, function, and disease risk. Stronger links between many environmental pollutants and disruptions to breast health continue to be documented in human populations, and there remain concerns that the methods utilized to identify, characterize, and prioritize these chemicals for risk assessment and risk management purposes are insufficient. There are also concerns that effects on the mammary gland have been largely ignored by regulatory agencies. Here, we provide technical guidance that is intended to enhance collection and evaluation of the mammary gland in mice and rats. We review several features of studies that should be controlled to properly evaluate the mammary gland, and then describe methods to appropriately collect the mammary gland from rodents. Furthermore, we discuss methods for preparing whole mounted mammary glands and numerous approaches that are available for the analysis of these samples. Finally, we conclude with several examples where analysis of the mammary gland revealed effects of environmental toxicants at low doses. Our work argues that the rodent mammary gland should be considered in chemical safety, hazard and risk assessments. It also suggests that improved measures of mammary gland outcomes, such as those we present in this review, should be included in the standardized methods evaluated by regulatory agencies such as the test guidelines used for identifying reproductive and developmental toxicants.

Automated summary

Research suggests that exposure to hormonally active chemicals during sensitive windows of development can impact mammary gland development, function, and disease risk. Stronger links between environmental pollutants and breast health disruptions continue to be found in human populations. This article provides technical guidance on collecting and evaluating the mammary gland in mice and rats, including methods for sample collection and analysis. The authors argue that the mammary gland should be considered in chemical safety assessments and recommend improved measures for evaluating mammary gland outcomes.