Isolation and the timing of mammary gland development, gonadarche, and ovarian senescence: implications for mammary tumor burden.

In this study of Norway rats, we hypothesized that lifelong psychosocial experiences, social isolation or group living, trigger different developmental trajectories in the ovarian system, contributing to predisease pathways for spontaneous mammary tumors. Epidemiological studies indicate that early puberty and delayed menopause are risk factors for breast cancer. To that end, we took a cross-sectional, prospective approach and examined the ovarian system at two developmental points, young adulthood and middle age. We assessed ovarian function at both points, as well as mammary gland development at puberty and mammary tumor burden in middle age. Social isolation dissociated two components of puberty; it accelerated maturation of ovarian function while it simultaneously delayed mammary tissue development thereby increasing the exposure of developing breast parenchyma to high levels of estrogen. By mid-life, socially isolated rats had greater tumor burden despite having entered estropause prematurely, demonstrating that isolation did not increase tumorigenesis by prolonging ovarian function. These findings are discussed in the context of facultative lifespan strategies for rats born at different times of year and those living in isolation or in a large burrow community.