The mouse mammary gland as a sentinel organ: distinguishing ‘control’ populations with diverse environmental histories

Abstract

BackgroundThere are numerous examples of laboratory animals that were inadvertently exposed to endocrine disrupting chemicals (EDCs) during the process of conducting experiments. Controlling contaminations in the laboratory is challenging, especially when their source is unknown. Unfortunately, EDC contaminations can interfere with the interpretation of data during toxicological evaluations. We propose that the male CD-1 mouse mammary gland is a sensitive bioassay to evaluate the inadvertent contamination of animal colonies.MethodsWe evaluated mammary glands collected from two CD-1 mouse populations with distinct environmental histories. Population 1 was born and raised in a commercial laboratory with unknown EDC exposures; Population 2 was the second generation raised in an animal facility with limited exposures to xenoestrogens from caging, feed, etc. Mammary glands were collected from all animals and evaluated using morphometric techniques to quantify morphological characteristics of the mammary gland.ResultsPopulation 1 (with suspected history of environmental chemical exposure) and Population 2 (with known limited history of xenoestrogen exposure) were morphologically distinguishable in adult males, prepubertal females, and pubertal females. Mammary glands from males raised in the commercial animal facility were significantly more developed, with larger ductal trees and more branching points. The appearance of these mammary glands was consistent with prior reports of male mice exposed to low doses of bisphenol A (BPA) during early development. In females, the two populations were morphologically distinct at both prepuberty and puberty, with the most striking differences observed in the number, size, and density of terminal end buds, e.g. highly proliferative structures found in the developing mammary gland.ConclusionsCollectively, these results suggest that the mouse mammary gland has the potential to be used as a sentinel organ to evaluate and distinguish animal colonies raised in different environmental conditions including potential EDC exposures. Our findings could help researchers that wish to perform a posteriori evaluations to determine whether inadvertent contamination with xenoestrogens (and potentially other EDCs) has occurred in their animal colonies, especially after new materials (feed, caging, water bottles) have been introduced. Finally, our results challenge the relatively common practice of using historical controls in toxicological experiments.

Postnatal exposure to a glyphosate-based herbicide modifies mammary gland growth and development in Wistar male rats

“…In recent years, the effects of endocrine-disrupting chemicals on the development of the male mammary gland of rodents has received increased attention due to its sensitive response to estrogenic and/or androgenic compounds (Altamirano et al, 2017;Filgo et al, 2016;Kass et al, 2015;Kolla et al, 2017;Mandrup et al, 2015;Vandenberg et al, 2013). In the current study, postnatal subacute exposure of male rats to GBH during a critical period of development resulted in alterations in the growth and development of the mammary gland in pre-and post-pubertal rats without systemic toxicity.…”

“…Therefore, the estrogenic potential effect of glyphosate remains under investigation. In general, new epidemiological and toxicological studies as well as human biomonitoring are urgently needed to determinate whether GBH could be considered an endocrine disruptor and to improve safety standard (Myers et al, 2016;Vandenberg et al, 2017).…”

An ovine model for investigation of the microenvironment of the male mammary gland

“…The gland thereafter regresses and at birth comprises minimal vestigial glandular tissue that lacks nipples (Cardiff et al, 2018;Pokharel et al, 2018;Szabo & Vandenberg, 2021). In some genetically modified mouse strains, glandular tissue can persist after birth (Pokharel et al, 2018;Szabo & Vandenberg, 2021) but may still lack key developmental structures required for mammary gland expansion such as terminal end buds (Kolla et al, 2017).…”

An ovine model for investigation of the microenvironment of the male mammary gland

“…The gland thereafter regresses and at birth comprises minimal vestigial glandular tissue that lacks nipples (Cardiff et al, 2018; Pokharel et al, 2018; Szabo and Vandenberg, 2021). In some genetically modified mouse strains, glandular tissue can persist after birth (Pokharel et al, 2018; Szabo and Vandenberg, 2021) but may still lack key developmental structures required for mammary gland expansion such as terminal end buds (Kolla et al, 2017).…”