Influences of neonatal environment on mammary gland development in female balb/c mice

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Objectives:  To understand how early life experiences influence normal and malignant mammary gland development Hypothesis:  It is hypothesized that early life events will differentially influence hormone levels (e.g. glucocorticoids and estrogen), altering breast development as measured by alterations in protein and gene expression patterns (e.g. estrogen receptor (ER), glucocorticoid receptor (GR), p53) and related gland morphology (measured by alterations in TEB or lobulo-alveolar numbers and branching patterns).  The interactions between environment, protein and gene expression and related mammary gland development may predispose the breast to increased risk of cancer development later in life. Scientific Approach:   The proposed studies will add to the limited data on how early social environment impacts on mammary gland development and future cancer risk.  Neonatal handling (H) and maternal separation (MS), two well established animal models of early-life environmental manipulations, differentially influence the development and life-time activity of several systems including the CNS, immune and neuroendocrine.  Because the mammary gland is one of a few organ systems that completes its development postnatally, it may be uniquely susceptible to genetic and epigenetic modifications caused by physiological alterations due to neonatal experiences. These studies are unique in that they are the first to systematically examine the influences of prepubertal experiences on mammary gland development, which in turn possibly directs the accumulation of mutagenic events, increasing breast cancer risk. A better understanding of the significant influence that the early social environment has on breast development, including alterations of breast cancer susceptibility genes, will improve our prospects for breast cancer prevention.