Lactational imprinting: exploiting a novel adaptive response to match milk supply to demand

哺乳印记：利用新颖的适应性反应来匹配牛奶供应与需求

• 批准号: 402453-2011
• 负责人: McFadden, Thomas
• 金额: $ 1.75万
• 依托单位: University of Alberta
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2011
• 资助国家: 加拿大
• 起止时间: 2011-01-01 至 2012-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=488069
• 关键词: Lactational; imprinting; exploiting; novel; adaptive

The long-term objective of this research is to identify and understand the key factors that regulate milk production by the bovine mammary gland in order to develop new and/or improved methods to enhance the efficiency of milk production. The current proposal is focused on understanding the response of the bovine mammary gland to increased milking frequency (4 times daily vs twice-daily milking) during early lactation. It is well established in mammals that mammary glands typically respond to increased suckling demand of their offspring by acutely increasing milk yield. Importantly, we and others have shown that the bovine udder is uniquely responsive during early lactation such that the increment in milk yield is partially carried over and persists through the remainder of that lactation. Little is known about the mechanisms underlying this response, however the novelty of the biology and the practical implications to the dairy industry are compelling. Over the past several years we have systematically studied this paradigm, mostly using a powerful, half-udder experimental model. We have identified ~ 20 genes as candidate regulators of the response that are coordinately regulated, suggesting a novel, adaptive pathway for modulating mammary function. We propose that the response is an example of "Lactational Imprinting" a novel biological program that regulates milk supply to meet demands of the offspring. The proposed research program is designed to discover: a) the function of specific candidate genes and their interactions in the novel putative adaptive response; b) the biological nature of the unique mammary gland response during early lactation; and c) the potential existence of lactational imprinting of key genes that lead to establishment of a new functional set point for milk yield. These studies will identify the mechanisms involved in the adaptive response to frequent milking and determine the function of individual genes/proteins that make up the putative novel lactational imprinting pathway. Findings are likely to be novel and relevant to other paradigms of adaptive physiology in other organs.

这项研究的长期目标是确定和了解调节牛乳腺产奶的关键因素，以便开发新的和/或改进的方法来提高产奶效率。 目前的提案重点是了解泌乳早期牛乳腺对增加挤奶频率（每天 4 次与每天两次）的反应。 在哺乳动物中，众所周知，乳腺通常通过急剧增加产奶量来应对其后代增加的哺乳需求。 重要的是，我们和其他人已经证明，牛乳房在泌乳早期具有独特的反应，因此产奶量的增加部分地延续下来并持续到泌乳的剩余时间。 人们对这种反应背后的机制知之甚少，但生物学的新颖性和对乳制品行业的实际影响是引人注目的。 在过去的几年里，我们系统地研究了这一范式，主要使用强大的半乳房实验模型。 我们已经确定了大约 20 个基因作为协调调节反应的候选调节因子，这表明了一种调节乳腺功能的新颖的适应性途径。 我们认为这种反应是“哺乳印记”的一个例子，这是一种新颖的生物程序，可以调节牛奶供应以满足后代的需求。 拟议的研究计划旨在发现：a）特定候选基因的功能及其在新的假定适应性反应中的相互作用； b) 哺乳早期独特乳腺反应的生物学性质； c) 关键基因的泌乳印记的潜在存在，导致建立新的产奶量功能设定点。这些研究将确定对频繁挤奶的适应性反应所涉及的机制，并确定构成假定的新型泌乳印记途径的单个基因/蛋白质的功能。 研究结果可能是新颖的，并且与其他器官的适应性生理学的其他范式相关。