Abstract

Ketosis is one of the most prevalent transition metabolic disorders in dairy cows, and has been intrinsically influenced by both genetic and nutritional factors. However, altered gene expression with respective to dairy cow ketosis has not been addressed yet, especially at the genome-wide level. In this study, we recruited nine Holsteins diagnosed with clinical ketosis and ten healthy controls, for which whole blood samples were collected at both prepartum and postpartum. Four groups of blood samples were defined: from cows with ketosis at prepartum (PCK, N = 9) and postpartum (CK, N = 9), respectively, and controls at prepartum (PHC, N = 10) and postpartum (HC, N = 10). RNA-Seq approach was used for investigating gene expression, by which a total of 27,233 genes were quantified with four billion high-quality reads. Subsequently, we revealed 75 and four differentially expressed genes (DEGs) between sick and control cows at postpartum and prepartum, respectively, which indicated that sick and control cows had similar gene expression patterns at prepartum. Meanwhile, there were 95 DEGs between postpartum and prepartum for sick cows, which showed depressed changes of gene expression during this transition period in comparison with healthy cows (428 DEGs). Functional analyses revealed the associated DEGs with ketosis were mainly involved in biological stress response, ion homeostasis, AA metabolism, energy signaling, and disease related pathways. Finally, we proposed that the expression level of STX1A would be potentially used as a new biomarker because it was the only gene that was highly expressed in sick cows at both prepartum and postpartum. These results could significantly help us to understand the underlying molecular mechanisms for incidence and progression of ketosis in dairy cows.

Highlights

  • Dairy cows, especially for high-production individuals, are very sensitive to metabolic diseases and environmental stresses during the periparturient period, because they are apt to suffer from negative energy balance (NEB) [1]

  • Previous reports have showed that elevation of BHBA in the systemic circulation contribute to metabolic acidosis [41], and metabolic acidosis is associated with minerals elements metabolism [16,42]

  • Results from healthy controls at postpartum (HC) group versus PHC group showed that the differentially expressed genes (DEGs) were primarily involved in ion homeostasis, fat digestion, and lipid metabolism; this is a finding that is similar to what has been reported using metabolomic analysis in transition cows [52]

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Summary

Introduction

Especially for high-production individuals, are very sensitive to metabolic diseases and environmental stresses during the periparturient period, because they are apt to suffer from negative energy balance (NEB) [1]. NEB in early-lactating cows is characterized by a failure of hepatic gluconeogenesis to supply adequate glucose for maintenance and lactation [2]. If the NEB-induced metabolic disorders could not be properly adapted and addressed, cows would develop into subclinical or clinical ketosis [3]. Ketosis is the most common metabolic disease in dairy cows during the periparturient period, with reported prevalence ranging from 6.9% to 43% [3,4,5]. Ketosis can significantly decrease milk production and reproduction efficiency, and increase the risk of displaced abomasum, lameness, and metritis [3,6].

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