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

本研究的长期目标是确定和了解牛乳腺调节产奶量的关键因素，以便开发新的和/或改进的方法来提高产奶量的效率。目前的建议侧重于了解在哺乳期早期，奶牛乳腺对增加挤奶频率（每天4次vs每天两次）的反应。在哺乳动物中，乳腺通常会通过急剧增加产奶量来对其后代增加的哺乳需求做出反应。重要的是，我们和其他人已经表明，牛的乳房在哺乳期早期具有独特的反应性，因此产奶量的增加部分被保留下来，并持续到哺乳期的剩余时间。人们对这种反应背后的机制知之甚少，然而，生物学的新颖性和对乳制品行业的实际影响是令人信服的。在过去的几年里，我们系统地研究了这一范式，主要是使用一个强大的半乳实验模型。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，这提示了调节乳腺功能的一种新的适应性途径。我们认为这种反应是“哺乳印记”的一个例子，这是一种新的生物程序，通过调节乳汁供应来满足后代的需求。提出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)哺乳期早期乳腺独特反应的生物学性质；c)可能存在的关键基因的哺乳期印记，导致建立一个新的功能设定值的产奶量。这些研究将确定频繁挤奶的适应性反应机制，并确定构成假定的新型哺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，并与其他器官的适应性生理学的其他范式相关。

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.