Psychosocial Stress Exposure Impairs Mammary Gland Development and Preserves Mammary Stem Cell Populations

Exposure to psychosocial stressors and ensuing stress physiology have been associated with invasive mammary tumors in rodent models of human breast cancer. Many physiologic and environmental exposures that influence breast cancer risk occur during mammary gland development. However, the effect of psychosocial stress exposure on mammary gland development remains unknown. In a nulliparous Sprague-Dawley rat model of breast cancer, we demonstrate that social isolation increased glucocorticoid reactivity to everyday stressors and reduced alveolobular differentiation during late puberty and young adulthood. Moreover, glucocorticoid stress reactivity and not reproductive steroid exposure was positively associated with the population of mammary progenitor and stem cells, which are the purported cell-of-origin in breast cancer. In vitro analysis demonstrated the glucocorticoid exposure decreased differentiation of mammary progenitor cells. The work in this thesis demonstrates that exposure to psychosocial stress and resulting elevated glucocorticoid reactivity disrupts both mammary gland growth and differentiation of mammary epithelium, which could contribute to a later increase in mammary cancer risk.