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

目的：为了了解早期生活经历如何影响正常和恶性乳腺发育假说：假设早期生活事件将不同地影响激素水平(例如糖皮质激素和雌激素)，通过蛋白质和基因表达模式(例如雌激素受体(ER)、糖皮质激素受体(GR)、P53)和相关腺体形态(通过TEB或小叶-肺泡数量和分支模式的变化来衡量)改变乳腺发育。环境、蛋白质和基因表达与相关乳腺发育之间的相互作用可能使乳房在以后的生活中患癌症的风险增加。科学方法：尽管拟议的研究将增加关于早期社会环境如何影响乳腺发育和未来癌症风险的有限数据。新生儿处理(H)和母体分离(MS)是两个成熟的早期环境操纵动物模型，它们对包括中枢神经系统、免疫和神经内分泌在内的几个系统的发育和一生活动产生不同的影响。由于乳腺是少数几个在出生后完成发育的器官系统之一，它可能唯一容易受到新生儿经历引起的生理变化引起的遗传和表观遗传改变的影响。这些研究的独特之处在于，它们首次系统地研究了青春期前经历对乳腺发育的影响，这反过来可能引导突变事件的积累，增加乳腺癌的风险。更好地了解早期社会环境对乳房发育的重大影响，包括乳腺癌易感基因的变化，将改善我们预防乳腺癌的前景。

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.