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Negative energy balance alters global gene expression and immune responses in the uterus of postpartum dairy cows.

Wathes DC, Cheng Z, Chowdhury W, Fenwick MA, Fitzpatrick R, Morris DG, Patton J, Murphy JJ - Physiol. Genomics (2009)

Bottom Line: White blood cell count and lymphocyte number were reduced in SNEB cows.Expression of several interferon-inducible genes including ISG20, IFIH1, MX1, and MX2 were also significantly increased in the SNEB cows.These results provide evidence that cows in SNEB were still undergoing an active uterine inflammatory response 2 wk postpartum, whereas MNEB cows had more fully recovered from their energy deficit, with their endometrium reaching a more advanced stage of repair.

View Article: PubMed Central - PubMed

Affiliation: Department of Veterinary Basic Sciences, Royal Veterinary College, London, United Kingdom. dcwathes@rvc.ac.uk

ABSTRACT
Most dairy cows suffer uterine microbial contamination postpartum. Persistent endometritis often develops, associated with reduced fertility. We used a model of differential feeding and milking regimes to produce cows in differing negative energy balance status in early lactation (mild or severe, MNEB or SNEB). Blood hematology was assessed preslaughter at 2 wk postpartum. RNA expression in endometrial samples was compared using bovine Affymetrix arrays. Data were mapped using Ingenuity Pathway Analysis. Circulating concentrations of IGF-I remained lower in the SNEB group, whereas blood nonesterified fatty acid and beta-hydroxybutyrate concentrations were raised. White blood cell count and lymphocyte number were reduced in SNEB cows. Array analysis of endometrial samples identified 274 differentially expressed probes representing 197 recognized genes between the energy balance groups. The main canonical pathways affected related to immunological and inflammatory disease and connective tissue disorders. Inflammatory response genes with major upregulation in SNEB cows included matrix metalloproteinases, chemokines, cytokines, and calgranulins. Expression of several interferon-inducible genes including ISG20, IFIH1, MX1, and MX2 were also significantly increased in the SNEB cows. These results provide evidence that cows in SNEB were still undergoing an active uterine inflammatory response 2 wk postpartum, whereas MNEB cows had more fully recovered from their energy deficit, with their endometrium reaching a more advanced stage of repair. SNEB may therefore prevent cows from mounting an effective immune response to the microbial challenge experienced after calving, prolonging the time required for uterine recovery and compromising subsequent fertility.

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IPA Network 4. Differentially regulated genes in endometrium involved in posttranslational modification, cell death, and connective tissue development and function with 13 focus molecules and a score of 23. The network is displayed graphically as nodes (gene/gene products) and edges (the biological relationship between nodes). The node color intensity indicates the expression of genes: red upregulated, green downregulated in SNEB vs. MNEB endometrium. The fold value and P values are indicated under each node. The shapes of nodes indicate the functional class of the gene product as shown in the key given in Fig. 2. Solid lines indicate a direct interaction, and dotted lines an indirect interaction.
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f5: IPA Network 4. Differentially regulated genes in endometrium involved in posttranslational modification, cell death, and connective tissue development and function with 13 focus molecules and a score of 23. The network is displayed graphically as nodes (gene/gene products) and edges (the biological relationship between nodes). The node color intensity indicates the expression of genes: red upregulated, green downregulated in SNEB vs. MNEB endometrium. The fold value and P values are indicated under each node. The shapes of nodes indicate the functional class of the gene product as shown in the key given in Fig. 2. Solid lines indicate a direct interaction, and dotted lines an indirect interaction.

Mentions: Network 4 (Fig. 5) also relates to connective tissue remodeling. MMP1, MMP9, and MMP13 were all highly upregulated in SNEB endometrium. The uterus must undergo extensive remodeling during the postpartum period. IL-8 is a major mediator of inflammatory responses and is also a potent angiogenic factor. Other genes associated with inflammation were VCAM1 and SELL, which are both involved with leukocyte-endothelial cell adhesion. MYB encodes a transcription factor that regulates progression through the cell cycle, and both this and the cyclin CCNB1 were downregulated in SNEB. Network 4 also featured the interferon-responsive genes MX2 and ISG20, in addition to DEFB1, which can also respond to viral infections. Differential expression of IFN genes themselves between groups was not detected, but three other IFN-inducible genes were differentially increased in endometrium of SNEB cows (MX1, IFIH1, and Loc512486; see Supplementary Table S2).


Negative energy balance alters global gene expression and immune responses in the uterus of postpartum dairy cows.

Wathes DC, Cheng Z, Chowdhury W, Fenwick MA, Fitzpatrick R, Morris DG, Patton J, Murphy JJ - Physiol. Genomics (2009)

IPA Network 4. Differentially regulated genes in endometrium involved in posttranslational modification, cell death, and connective tissue development and function with 13 focus molecules and a score of 23. The network is displayed graphically as nodes (gene/gene products) and edges (the biological relationship between nodes). The node color intensity indicates the expression of genes: red upregulated, green downregulated in SNEB vs. MNEB endometrium. The fold value and P values are indicated under each node. The shapes of nodes indicate the functional class of the gene product as shown in the key given in Fig. 2. Solid lines indicate a direct interaction, and dotted lines an indirect interaction.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2747344&req=5

f5: IPA Network 4. Differentially regulated genes in endometrium involved in posttranslational modification, cell death, and connective tissue development and function with 13 focus molecules and a score of 23. The network is displayed graphically as nodes (gene/gene products) and edges (the biological relationship between nodes). The node color intensity indicates the expression of genes: red upregulated, green downregulated in SNEB vs. MNEB endometrium. The fold value and P values are indicated under each node. The shapes of nodes indicate the functional class of the gene product as shown in the key given in Fig. 2. Solid lines indicate a direct interaction, and dotted lines an indirect interaction.
Mentions: Network 4 (Fig. 5) also relates to connective tissue remodeling. MMP1, MMP9, and MMP13 were all highly upregulated in SNEB endometrium. The uterus must undergo extensive remodeling during the postpartum period. IL-8 is a major mediator of inflammatory responses and is also a potent angiogenic factor. Other genes associated with inflammation were VCAM1 and SELL, which are both involved with leukocyte-endothelial cell adhesion. MYB encodes a transcription factor that regulates progression through the cell cycle, and both this and the cyclin CCNB1 were downregulated in SNEB. Network 4 also featured the interferon-responsive genes MX2 and ISG20, in addition to DEFB1, which can also respond to viral infections. Differential expression of IFN genes themselves between groups was not detected, but three other IFN-inducible genes were differentially increased in endometrium of SNEB cows (MX1, IFIH1, and Loc512486; see Supplementary Table S2).

Bottom Line: White blood cell count and lymphocyte number were reduced in SNEB cows.Expression of several interferon-inducible genes including ISG20, IFIH1, MX1, and MX2 were also significantly increased in the SNEB cows.These results provide evidence that cows in SNEB were still undergoing an active uterine inflammatory response 2 wk postpartum, whereas MNEB cows had more fully recovered from their energy deficit, with their endometrium reaching a more advanced stage of repair.

View Article: PubMed Central - PubMed

Affiliation: Department of Veterinary Basic Sciences, Royal Veterinary College, London, United Kingdom. dcwathes@rvc.ac.uk

ABSTRACT
Most dairy cows suffer uterine microbial contamination postpartum. Persistent endometritis often develops, associated with reduced fertility. We used a model of differential feeding and milking regimes to produce cows in differing negative energy balance status in early lactation (mild or severe, MNEB or SNEB). Blood hematology was assessed preslaughter at 2 wk postpartum. RNA expression in endometrial samples was compared using bovine Affymetrix arrays. Data were mapped using Ingenuity Pathway Analysis. Circulating concentrations of IGF-I remained lower in the SNEB group, whereas blood nonesterified fatty acid and beta-hydroxybutyrate concentrations were raised. White blood cell count and lymphocyte number were reduced in SNEB cows. Array analysis of endometrial samples identified 274 differentially expressed probes representing 197 recognized genes between the energy balance groups. The main canonical pathways affected related to immunological and inflammatory disease and connective tissue disorders. Inflammatory response genes with major upregulation in SNEB cows included matrix metalloproteinases, chemokines, cytokines, and calgranulins. Expression of several interferon-inducible genes including ISG20, IFIH1, MX1, and MX2 were also significantly increased in the SNEB cows. These results provide evidence that cows in SNEB were still undergoing an active uterine inflammatory response 2 wk postpartum, whereas MNEB cows had more fully recovered from their energy deficit, with their endometrium reaching a more advanced stage of repair. SNEB may therefore prevent cows from mounting an effective immune response to the microbial challenge experienced after calving, prolonging the time required for uterine recovery and compromising subsequent fertility.

Show MeSH
Related in: MedlinePlus