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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 2. Differentially regulated genes in endometrium involved in cellular movement, hematological system development and function and immune cell trafficking with 20 focus molecules and a score of 40. 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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f3: IPA Network 2. Differentially regulated genes in endometrium involved in cellular movement, hematological system development and function and immune cell trafficking with 20 focus molecules and a score of 40. 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 2 (Fig. 3) showed strong associations with the EB model used as the basis of the experiment, in which plasma concentrations of IGF-I were reduced, while NEFA was greatly elevated. Local endometrial expression of IGF-I was also reduced, whereas IGFBP1 was increased in SNEB cows. Associations between these genes are shown with plasma GH and insulin and STAT5, a transcription factor that is phosphorylated in response to cytokine signaling. Network 2 also featured signaling of the proinflammatory cytokine IL-1 and linked this to prostaglandin production, as PTGS1 and PTGS2 were both higher in SNEB cows. CD36 encodes a protein found on platelets that acts as a receptor for thrombospondins, which are involved in cell adhesion processes. CD36 also binds to collagen, anionic phospholipids and oxidized LDL and may play a role in fatty acid transport. The fatty acid binding protein FABP4 was also upregulated whereas GSTA1 (glutathione S-transferase) was decreased. GSTA1 can detoxify products of oxidative stress, providing protection from reactive oxygen species and the products of peroxidation. These changes may be related to the raised NEFA concentrations. CXCL13 and CXCL14 are attractants for B cells and monocytes, respectively. This network also included the antimicrobial calgranulin genes S100A8 and S100A9, which were both highly increased 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 2. Differentially regulated genes in endometrium involved in cellular movement, hematological system development and function and immune cell trafficking with 20 focus molecules and a score of 40. 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

f3: IPA Network 2. Differentially regulated genes in endometrium involved in cellular movement, hematological system development and function and immune cell trafficking with 20 focus molecules and a score of 40. 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 2 (Fig. 3) showed strong associations with the EB model used as the basis of the experiment, in which plasma concentrations of IGF-I were reduced, while NEFA was greatly elevated. Local endometrial expression of IGF-I was also reduced, whereas IGFBP1 was increased in SNEB cows. Associations between these genes are shown with plasma GH and insulin and STAT5, a transcription factor that is phosphorylated in response to cytokine signaling. Network 2 also featured signaling of the proinflammatory cytokine IL-1 and linked this to prostaglandin production, as PTGS1 and PTGS2 were both higher in SNEB cows. CD36 encodes a protein found on platelets that acts as a receptor for thrombospondins, which are involved in cell adhesion processes. CD36 also binds to collagen, anionic phospholipids and oxidized LDL and may play a role in fatty acid transport. The fatty acid binding protein FABP4 was also upregulated whereas GSTA1 (glutathione S-transferase) was decreased. GSTA1 can detoxify products of oxidative stress, providing protection from reactive oxygen species and the products of peroxidation. These changes may be related to the raised NEFA concentrations. CXCL13 and CXCL14 are attractants for B cells and monocytes, respectively. This network also included the antimicrobial calgranulin genes S100A8 and S100A9, which were both highly increased 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