Systems approach to deciphering molecular mechanisms of infertility in lactating dairy cows with subclinical ketosis

可持续的奶牛生产是奶牛长寿的一项功能。减少寿命是无利可图的，因为减少了终生产奶量，而且在环境上也是不可持续的，因为必须在牛群中保留更多的替代小母牛。生殖障碍，从根本上说是由于卵巢功能障碍，是头号原因的扑杀。因此，迫切需要了解卵巢功能障碍的机制，以制定诊断、治疗和管理策略，以优化奶牛的繁殖性能。长期以来，奶牛在哺乳早期所经历的代谢应激被认为会对生殖过程产生负面影响。亚临床酮症(SCK)是奶牛最常见的代谢紊乱。我们假设与SCK相关的代谢改变对卵泡基因的表达有独特的影响。本项目的目的是确定健康奶牛和SCK奶牛肝脏和卵巢颗粒细胞的代谢和激素水平以及基因表达谱。这些目标与我们的行业合作伙伴Novalait的研究重点“奶牛繁殖和繁殖”保持一致。我们建议使用系统生物学的方法，结合RNA测序技术、分子生物学和生物信息学工具来研究健康奶牛和SCK奶牛的肝脏和卵巢功能。其他分子生物学技术和农场数据，包括生产、营养、繁殖和淘汰率，也将被用于将代谢扰动与卵巢功能障碍联系起来。该项目的结果将加深我们对SCK对卵巢功能的影响的理解，从而提高奶牛的生育能力。产生的数据可能有助于识别牛奶中的标记集，从而预测奶牛患有SCK和随后的生殖功能障碍。这些标记可以用来建议农民奶牛有潜在的生殖问题，需要适当的干预，以最好地实现生育和长寿。

Sustainable dairy production is a function of dairy cow longevity. Reduced longevity is not profitable because of reduced lifetime milk yield and it is environmentally unsustainable because more replacement heifers have to be maintained in the herd. Reproductive failure, which is fundamentally due to ovarian dysfunction, is the number one cause of culling. Therefore, understanding the mechanisms of ovarian dysfunction is urgently needed to develop diagnostic, therapeutic and managemental strategies to optimize reproductive performance of lactating dairy cows. The metabolic stress that the cows experience during early lactation has long been proposed to negatively impact reproductive processes. Subclinical ketosis (SCK) is the most prevalent metabolic disorder in dairy herds. We hypothesize that metabolic alterations associated with SCK have unique effects on ovarian follicular gene expression. The objective of this project are to determine metabolic and hormonal levels and to profile gene expression in the liver and ovarian granulosa cells of healthy and SCK cows. These objectives are aligned with the research priority, "Dairy cattle fertility and reproduction" of our industry partner, Novalait. We propose to use systems biology approach employing RNA sequencing technology, molecular biology and bioinformatics tools to investigate the liver and ovarian functions in healthy and SCK cows. Other molecular biology techniques and on-farm data including production, nutritional, reproduction and culling rate will also be used link metabolic perturbation to ovarian dysfunction. The results of this project will enhance our understanding of the impact of SCK on ovarian functions and thus lactating cow fertility. The data generated may contribute to identification of marker sets in milk that will predict cows suffering from SCK and consequent reproductive dysfunction. Such markers could be used to advise farmers of the cows with potential reproductive problems and needing appropriate intervention to best achieve fertility and longevity.