Toward a digital analysis of environmental impacts on rodent mammary gland density during critical developmental windows

Alina M Hamilton; Linnea T Olsson; Bentley R Midkiff; Elena Morozova; Yanrong Su; Sandra Z Haslam; Laura N Vandenberg; Sallie S Schneider; Julia Santucci-Pereira; D Joseph Jerry; Melissa A Troester; Richard C Schwartz

doi:10.1016/j.reprotox.2022.06.002

Toward a digital analysis of environmental impacts on rodent mammary gland density during critical developmental windows

Reprod Toxicol. 2022 Aug:111:184-193. doi: 10.1016/j.reprotox.2022.06.002. Epub 2022 Jun 8.

Authors

Affiliations

¹ Department of Pathology and Laboratory Medicine, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
² Department of Epidemiology, Gillings School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
³ Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
⁴ Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI, USA.
⁵ The Irma H. Russo MD Breast Cancer Research Laboratory, Fox Chase Cancer Center, Temple University Health System, Philadelphia, PA, USA.
⁶ Department of Physiology, Michigan State University, East Lansing, MI, USA.
⁷ Department of Environmental Health Sciences, University of Massachusetts, Amherst, MA, USA.
⁸ Pioneer Valley Life Sciences Institute, Springfield, MA, USA; Department of Surgery, University of Massachusetts Medical School-Baystate, Springfield, MA, USA.
⁹ Pioneer Valley Life Sciences Institute, Springfield, MA, USA; Department of Veterinary and Animal Sciences, University of Massachusetts Amherst, Amherst, MA, USA.
¹⁰ Department of Epidemiology, Gillings School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
¹¹ Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI, USA. Electronic address: schwart9@msu.edu.

Abstract

While mammographic breast density is associated with breast cancer risk in humans, there is no comparable surrogate risk measure in mouse and rat mammary glands following various environmental exposures. In the current study, mammary glands from mice and rats subjected to reproductive factors and exposures to environmental chemicals that have been shown to influence mammary gland development and/or susceptibility to mammary tumors were evaluated for histologic density by manual and automated digital methods. Digital histological density detected changes due to hormonal stimuli/reproductive factors (parity), dietary fat, and exposure to environmental chemicals, such as benzophenone-3 and a combination of perfluorooctanoic acid and zeranol. Thus, digital analysis of mammary gland density offers a high throughput method that can provide a highly reproducible means of comparing a measure of histological density across independent experiments, experimental systems, and laboratories. This methodology holds promise for the detection of environmental impacts on mammary gland structure in mice and rats that may be comparable to human breast density, thus potentially allowing comparisons between rodent models and human breast cancer studies.

Keywords: Benzophenone-3; Breast cancer; Digital histology; High fat diet; Mammary density; Parity; Perfluorooctanoic acid; Zeranol.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Breast Density
Breast Neoplasms*
Environment
Female
Humans
Mammary Glands, Animal*
Mice
Pregnancy
Rats
Rodentia

Abstract

Publication types

MeSH terms

Grants and funding