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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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Related in: MedlinePlus

IPA Network 3. Differentially regulated genes in endometrium involved in hematological system development and function, humoral immune response, and tissue morphology with 17 focus molecules and a score of 29. 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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f4: IPA Network 3. Differentially regulated genes in endometrium involved in hematological system development and function, humoral immune response, and tissue morphology with 17 focus molecules and a score of 29. 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 3 (Fig. 4) was also identified as having a role in hematological system development and function. It featured a number of genes involved in T cell development and activation (CD69, CCR5, CCR7, PTPN22, ZAP70). T cells play a key role in inflammation and tissue remodeling through activation of MMPs that break down extracellular matrix. MMP3 encodes an enzyme that degrades fibronectin, laminin, and several types of collagen and is thought to be of particular importance in wound repair. MMP3 is linked to PLAUR, the receptor for urokinase plasminogen activator. PLAU converts plasminogen to plasmin, the active form of a proteolytic enzyme that plays an important initial step in MMP activation. This pathway is activated through a MAP kinase signaling cascade and MAK3K8 and MAPK13 were both upregulated in SNEB.


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 3. Differentially regulated genes in endometrium involved in hematological system development and function, humoral immune response, and tissue morphology with 17 focus molecules and a score of 29. 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

f4: IPA Network 3. Differentially regulated genes in endometrium involved in hematological system development and function, humoral immune response, and tissue morphology with 17 focus molecules and a score of 29. 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 3 (Fig. 4) was also identified as having a role in hematological system development and function. It featured a number of genes involved in T cell development and activation (CD69, CCR5, CCR7, PTPN22, ZAP70). T cells play a key role in inflammation and tissue remodeling through activation of MMPs that break down extracellular matrix. MMP3 encodes an enzyme that degrades fibronectin, laminin, and several types of collagen and is thought to be of particular importance in wound repair. MMP3 is linked to PLAUR, the receptor for urokinase plasminogen activator. PLAU converts plasminogen to plasmin, the active form of a proteolytic enzyme that plays an important initial step in MMP activation. This pathway is activated through a MAP kinase signaling cascade and MAK3K8 and MAPK13 were both upregulated in SNEB.

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