The postpartum endometrial inflammatory response: a normal physiological event with potential implications for bovine fertility

Abstract

<jats:p>After calving, the bovine endometrium undergoes marked morphological and functional changes that are necessary for subsequent re-breeding. Regulation and integration of these key events are largely uncharacterised. Here, endometrial swabs and biopsies were taken at 15, 30 and 60 days postpartum (DPP) from 13 healthy primiparous cows, 10 of which subsequently conceived, with a view to characterising innate and inflammatory gene expression profiles. Endometrial biopsies exhibited severe inflammation (&gt;75 leukocytes per high-power field) at 15 DPP, which had begun to resolve by 30 DPP and had completely resolved by 60 DPP. The severe inflammation at 15 DPP coincided with uterine infection in all cows and a significant increase (P &lt; 0.05) in the expression of all of 16 genes investigated, including CD45, IL8, IL6, IL1, TNF, TAP, SAA3 and HP at 15 DPP, relative to 60 DPP. All of these parameters had begun to return to normal physiological levels at 30 DPP. Systemically, serum protein concentrations of IL-8 were elevated at 15 DPP compared with 60 DPP (78 pg mL–1 vs 48 pg mL–1; P = 0.02). These results indicate that endometrial inflammation, leukocyte infiltration and increased expression of pro-inflammatory, antimicrobial and acute-phase protein genes are expected features of the postpartum period, critical to bacterial clearance and uterine involution.</jats:p>

Endometrial epithelial cells are potent producers of tracheal antimicrobial peptide and serum amyloid A3 gene expression in response to E. coli stimulation

“…The early increase in expression of IL-8 (19-fold after 6 h and 13-fold after 24 h; P < 0.05, Fig. 1) demonstrates the ability of these cells to detect and respond to bacterial antigens, in agreement with earlier work by our group ( Chapwanya et al, 2009 andChapwanya et al, 2012), and by others ( Davies et al, 2008 andPalffy et al, 2009). Twenty four hours post-stimulation, gene expression for IL8 and the inflammatory cytokines have reduced to levels less than those after 6 h (Fig.…”

“…Innate immunity is the first line of host defence against invading pathogens ( Medzhitov and Janeway, 2000, O'Neill, 2001, O'Neill, 2005and Palsson-McDermott and O'Neill, 2007. We have recently characterised innate immune gene expression in uterine tissue from cows that had experienced endometrial bacterial invasion and inflammation postpartum ( Chapwanya et al, 2009 andChapwanya et al, 2012). Genes encoding defence molecules such as antimicrobial peptides (AMPs) and acute phase proteins (APPs) were expressed in endometrial biopsies.…”

Innate immunity and inflammation of the bovine female reproductive tract in health and disease

“…Furthermore, there are temporal changes in the expression of transcripts for IL1B, IL6, CXCL8, TNF, CXCL5, HP and PTGS2 during the postpartum period, with peak expression on day 17 after parturition . These temporal changes in gene expression reflect the histological evidence of inflammation during the first 3 weeks postpartum, which resolves by 40-60 days after parturition (Bonnett et al 1991, Chapwanya et al 2012. As well as increased gene expression, postpartum cows, particularly if the endometrium is infected, have increased protein abundance of S100A8 and S100A9 in the epithelium and stroma, as well as in immune cells, as determined by immunohistochemistry (Swangchan-Uthai et al 2013).…”

Interactions between negative energy balance, metabolic diseases, uterine health and immune response in transition dairy cows

“…The process seems to be driven in part by bacterial invasion (Chapwanya et al, 2012). Under normal circumstances the number of cows with bacterial infection at 3 weeks postpartum should decline to 40% (Sheldon, 2004).…”