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RESEARCH ARTICLE

Increased mRNA expression of selected pro-inflammatory factors in inflamed bovine endometrium in vivo as well as in endometrial epithelial cells exposed to Bacillus pumilus in vitro

Martina A. Gärtner A , Sarah Peter A , Markus Jung B , Marc Drillich C , Ralf Einspanier A and Christoph Gabler A D
+ Author Affiliations
- Author Affiliations

A Institute of Veterinary Biochemistry, Freie Universität Berlin, Oertzenweg 19b, 14163 Berlin, Germany.

B Institute for the Reproduction of Farm Animals Schönow, Bernauer Allee 10, 16321 Bernau, Germany.

C University Clinic for Ruminants, Clinical Unit for Herd Health Management in Ruminants, Vetmeduni Vienna, Veterinärplatz 1, 1210 Vienna, Austria.

D Corresponding author. Email: christoph.gabler@fu-berlin.de

Reproduction, Fertility and Development 28(7) 982-994 https://doi.org/10.1071/RD14219
Submitted: 19 June 2014  Accepted: 14 November 2014   Published: 7 January 2015

Abstract

Endometrial epithelium plays a crucial role in the first immune response to invading bacteria by producing cytokines and chemokines. The aim of this study was to investigate the first inflammatory response of the endometrium in vivo and in vitro. Gene expression of several pro-inflammatory factors and Toll-like receptors (TLR2, -4, -6) was determined in endometrial cytobrush samples obtained from healthy cows and cows with clinical or subclinical endometritis. Endometrial epithelial cells were co-cultured with an isolated autochthonous uterine bacterial strain Bacillus pumilus. Total RNA was extracted from in vivo and in vitro samples and subjected to real-time reverse transcription polymerase chain reaction. CXC ligands (CXCL) 1/2 and CXC chemokine receptor (CXCR) 2 mRNA expression was higher in cows with subclinical endometritis and CXCL3 mRNA expression was higher in cows with clinical endometritis compared with healthy cows. B. pumilus induced cell death of epithelial cells within 24 h of co-culturing. The presence of B. pumilus resulted in significantly higher mRNA expression of interleukin 1α (IL1A), IL6, IL8, CXCL1–3 and prostaglandin–endoperoxide synthase 2 in co-cultured cells compared with untreated controls. The maximum increase was mainly detected after 2 h. These results support the hypothesis that bacterial infection of endometrial cells might induce prompt synthesis of pro-inflammatory cytokines resulting in a local inflammatory reaction.

Additional keywords: bovine endometritis, CXC ligands, interleukins, Toll-like receptors.


References

Addison, C. L., Daniel, T. O., Burdick, M. D., Liu, H., Ehlert, J. E., Xue, Y. Y., Buechi, L., Walz, A., Richmond, A., and Strieter, R. M. (2000). The CXC chemokine receptor 2, CXCR2, is the putative receptor for ELR+ CXC chemokine-induced angiogenic activity. J. Immunol. 165, 5269–5277.
The CXC chemokine receptor 2, CXCR2, is the putative receptor for ELR+ CXC chemokine-induced angiogenic activity.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3cXnvVOnt7k%3D&md5=c21e6441a95a4c7bd28df9818d82b2f7CAS | 11046061PubMed |

Amos, M. R., Healey, G. D., Goldstone, R. J., Mahan, S. M., Düvel, A., Schuberth, H.-J., Sandra, O., Zieger, P., Dieuzy-Labaye, I., Smith, D. G., and Sheldon, I. M. (2014). Differential endometrial cell sensitivity to a cholesterol-dependent cytolysin links Trueperella pyogenes to uterine disease in cattle. Biol. Reprod. 90, 54.
Differential endometrial cell sensitivity to a cholesterol-dependent cytolysin links Trueperella pyogenes to uterine disease in cattle.Crossref | GoogleScholarGoogle Scholar | 24478394PubMed |

Arosh, J. A., Parent, J., Chapdelaine, P., Sirois, J., and Fortier, M. A. (2002). Expression of cyclooxygenases 1 and 2 and prostaglandin E synthase in bovine endometrial tissue during the oestrous cycle. Biol. Reprod. 67, 161–169.
Expression of cyclooxygenases 1 and 2 and prostaglandin E synthase in bovine endometrial tissue during the oestrous cycle.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD38XkvV2itL0%3D&md5=8b75be00ce543e779a48c8c558e42be8CAS | 12080013PubMed |

Barański, W., Łukasik, K., Skarżyński, D., Sztachanska, M., Zdunczyk, S., and Janowski, T. (2013). Secretion of prostaglandins and leukotrienes by endometrial cells in cows with subclinical and clinical endometritis. Theriogenology 80, 766–772.
Secretion of prostaglandins and leukotrienes by endometrial cells in cows with subclinical and clinical endometritis.Crossref | GoogleScholarGoogle Scholar | 23932172PubMed |

Barbosa, T. M., Serra, C. R., La Ragione, R. M., Woodward, M. J., and Henriques, A. O. (2005). Screening for bacillus isolates in the broiler gastrointestinal tract. Appl. Environ. Microbiol. 71, 968–978.
Screening for bacillus isolates in the broiler gastrointestinal tract.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXhsVKgt70%3D&md5=1b9a579a174d24f7d39a9ea3a1c6543fCAS | 15691955PubMed |

Baston-Büst, D. M., Schanz, A., Böddeker, S. J., Altergot-Ahmad, O., Krüssel, J.-S., Rein, D., and Hess, A. P. (2013). CXCL1 expression in human decidua in vitro is mediated via the MAPK signalling cascade. Cytokine 64, 79–85.
CXCL1 expression in human decidua in vitro is mediated via the MAPK signalling cascade. Crossref | GoogleScholarGoogle Scholar | 23953856PubMed |

Bauersachs, S., and Wolf, E. (2013). Immune aspects of embryo–maternal cross-talk in the bovine uterus. J. Reprod. Immunol. 97, 20–26.
Immune aspects of embryo–maternal cross-talk in the bovine uterus.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3sXivFyisb8%3D&md5=c40b02fe1965d3cfa5b841044e6c8631CAS | 23432868PubMed |

Bell, M. J., Hallenbeck, J. M., and Gallo, V. (2004). Determining the fetal inflammatory response in an experimental model of intrauterine inflammation in rats. Pediatr. Res. 56, 541–546.
Determining the fetal inflammatory response in an experimental model of intrauterine inflammation in rats.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2cXnsFGqsLo%3D&md5=f1e578d90bc1c6174c52abf1b8ed5e1fCAS | 15295096PubMed |

Betts, J. G., and Hansen, P. J. (1992). Regulation of prostaglandin secretion from epithelial and stromal cells of the bovine endometrium by interleukin-1 beta, interleukin-2, granulocyte–macrophage colony-stimulating factor and tumour necrosis factor-alpha. Life Sci. 51, 1171–1176.
Regulation of prostaglandin secretion from epithelial and stromal cells of the bovine endometrium by interleukin-1 beta, interleukin-2, granulocyte–macrophage colony-stimulating factor and tumour necrosis factor-alpha.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK38Xls1Clt78%3D&md5=eb376c66ed19559263af6e33f1bb9f3dCAS | 1518379PubMed |

Bonnett, B. N., Martin, S. W., Gannon, V. P., Miller, R. B., and Etherington, W. G. (1991). Endometrial biopsy in Holstein–Friesian dairy cows. III. Bacteriological analysis and correlations with histological findings. Can. J. Vet. Res. 55, 168–173.
| 1:STN:280:DyaK3Mzls1ChtQ%3D%3D&md5=276c3f6d0e96fcb5f0596d37b464afdbCAS | 1884297PubMed |

Borges, A. M., Healey, G. D., and Sheldon, I. M. (2012). Explants of intact endometrium to model bovine innate immunity and inflammation ex vivo. Am. J. Reprod. Immunol. 67, 526–539.
Explants of intact endometrium to model bovine innate immunity and inflammation ex vivo.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38XhtVClsb7E&md5=bd601e6cd076360ad1e62b3b46e42385CAS | 22324889PubMed |

Bustin, S. A., Benes, V., Garson, J. A., Hellemans, J., Huggett, J., Kubista, M., Mueller, R., Nolan, T., Pfaffl, M. W., Shipley, G. L., Vandesompele, J., and Wittwer, C. T. (2009). The MIQE guidelines: minimum information for publication of quantitative real-time PCR experiments. Clin. Chem. 55, 611–622.
The MIQE guidelines: minimum information for publication of quantitative real-time PCR experiments.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXktVWqs7g%3D&md5=51e64ac42595f31e7d9b607232abed5cCAS | 19246619PubMed |

Chapwanya, A., Meade, K. G., Doherty, M. L., Callanan, J. J., Mee, J. F., and O’Farrelly, C. (2009). Histopathological and molecular evaluation of Holstein–Friesian cows postpartum: toward an improved understanding of uterine innate immunity. Theriogenology 71, 1396–1407.
Histopathological and molecular evaluation of Holstein–Friesian cows postpartum: toward an improved understanding of uterine innate immunity.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXltl2murw%3D&md5=b98456e63568d84dbb9a5d14d62fe077CAS | 19233457PubMed |

Chapwanya, A., Meade, K. G., Doherty, M. L., Callanan, J. J., and O’Farrelly, C. (2013). Endometrial epithelial cells are potent producers of tracheal antimicrobial peptide and serum amyloid A3 gene expression in response to E. coli stimulation. Vet. Immunol. Immunopathol. 151, 157–162.
Endometrial epithelial cells are potent producers of tracheal antimicrobial peptide and serum amyloid A3 gene expression in response to E. coli stimulation.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38XhslymsbbI&md5=a287e7688b7da375aa4b340061a11e4bCAS | 23200820PubMed |

Cronin, J. G., Turner, M. L., Goetze, L., Bryant, C. E., and Sheldon, I. M. (2012). Toll-like receptor 4 and MYD88-dependent signalling mechanisms of the innate immune system are essential for the response to lipopolysaccharide by epithelial and stromal cells of the bovine endometrium. Biol. Reprod. 86, 51.
Toll-like receptor 4 and MYD88-dependent signalling mechanisms of the innate immune system are essential for the response to lipopolysaccharide by epithelial and stromal cells of the bovine endometrium.Crossref | GoogleScholarGoogle Scholar | 22053092PubMed |

Davies, D., Meade, K., Herath, S., Eckersall, P., Gonzalez, D., White, J., Conlan, R., O’Farrelly, C., and Sheldon, I. M. (2008). Toll-like receptor and antimicrobial peptide expression in the bovine endometrium. Reprod. Biol. Endocrinol. 6, 53.
Toll-like receptor and antimicrobial peptide expression in the bovine endometrium.Crossref | GoogleScholarGoogle Scholar | 19017375PubMed |

Dinarello, C. A., Simon, A., and van der Meer, J. W. M. (2012). Treating inflammation by blocking interleukin-1 in a broad spectrum of diseases. Nat. Rev. Drug Discov. 11, 633–652.
Treating inflammation by blocking interleukin-1 in a broad spectrum of diseases.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38XhtFWmtrfJ&md5=ec3ff0d5596e6dedc17f2bc1764c3f8cCAS | 22850787PubMed |

Dolezel, R., Palenik, T., Cech, S., Kohoutova, L., and Vyskocil, M. (2010). Bacterial contamination of the uterus in cows with various clinical types of metritis and endometritis and use of hydrogen peroxide for intrauterine treatment. Vet. Med. (Praha) 55, 504–511.

Dubuc, J., Duffield, T. F., Leslie, K. E., Walton, J. S., and LeBlanc, S. J. (2010). Definitions and diagnosis of postpartum endometritis in dairy cows. J. Dairy Sci. 93, 5225–5233.
Definitions and diagnosis of postpartum endometritis in dairy cows.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXnsl2rsQ%3D%3D&md5=f83e484f036269599c91f9dae5b4acd5CAS | 20965337PubMed |

Fischer, C., Drillich, M., Odau, S., Heuwieser, W., Einspanier, R., and Gabler, C. (2010). Selected pro-inflammatory factor transcripts in bovine endometrial epithelial cells are regulated during the oestrous cycle and elevated in case of subclinical or clinical endometritis. Reprod. Fertil. Dev. 22, 818–829.
Selected pro-inflammatory factor transcripts in bovine endometrial epithelial cells are regulated during the oestrous cycle and elevated in case of subclinical or clinical endometritis.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXlsVCqtL0%3D&md5=e7fe90d46a692abc2fd6f74a96a4b166CAS | 20450834PubMed |

Fakhry, S., Sorrentini, I., Ricca, E., de Felice, M., and Baccigalupi, L. (2008). Characterization of spore forming Bacilli isolated from the human gastrointestinal tract. J. Appl. Microbiol. 105, 2178–2186.
Characterization of spore forming Bacilli isolated from the human gastrointestinal tract.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXptFKmsw%3D%3D&md5=4f3331f9534c93d7ff0f36d42d7ef88eCAS | 19120663PubMed |

Fortier, M. A., Guilbault, L. A., and Grasso, F. (1988). Specific properties of epithelial and stromal cells from the endometrium of cows. J. Reprod. Fertil. 83, 239–248.
Specific properties of epithelial and stromal cells from the endometrium of cows.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaL1cXksV2jurY%3D&md5=c6ebd7d5c2a99c9844c68348995aacfaCAS | 3165129PubMed |

Fortier, M. A., Krishnaswamy, K., Danyod, G., Boucher-Kovalik, S., and Chapdalaine, P. (2008). A postgenomic integrated view of prostaglandins in reproduction: implications for other body systems. J. Physiol. Pharmacol. 59, 65–89.
| 18802217PubMed |

From, C., Hormazabal, V., and Granum, P. E. (2007). Food poisoning associated with pumilacidin-producing Bacillus pumilus in rice. Int. J. Food Microbiol. 115, 319–324.
Food poisoning associated with pumilacidin-producing Bacillus pumilus in rice.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXjtFGisrY%3D&md5=0c3ad4e7f3663733c9114d0e112c0419CAS | 17275116PubMed |

Gabler, C., Drillich, M., Fischer, C., Holder, C., Heuwieser, W., and Einspanier, R. (2009). Endometrial expression of selected transcripts involved in prostaglandin synthesis in cows with endometritis. Theriogenology 71, 993–1004.
Endometrial expression of selected transcripts involved in prostaglandin synthesis in cows with endometritis.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXivVWltb4%3D&md5=4ae8f769215c9ad147e42cc8ebeb0bacCAS | 19162311PubMed |

Gabler, C., Fischer, C., Drillich, M., Einspanier, R., and Heuwieser, W. (2010). Time-dependent mRNA expression of selected pro-inflammatory factors in the endometrium of primiparous cows postpartum. Reprod. Biol. Endocrinol. 8, 152.
Time-dependent mRNA expression of selected pro-inflammatory factors in the endometrium of primiparous cows postpartum.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXjtlehtw%3D%3D&md5=98f2b3a34f3fb8525980812accdf1361CAS | 21176181PubMed |

Ghasemi, F., Gonzalez-Cano, P., Griebel, P. J., and Palmer, C. (2012). Pro-inflammatory cytokine gene expression in endometrial cytobrush samples harvested from cows with and without subclinical endometritis. Theriogenology 78, 1538–1547.
Pro-inflammatory cytokine gene expression in endometrial cytobrush samples harvested from cows with and without subclinical endometritis.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38Xht1Kju73L&md5=45f603df81a8ebcd8f8c01b9fa06d912CAS | 22925636PubMed |

Gilbert, R. O., Shin, S. T., Guard, C. L., Erb, H. N., and Frajblat, M. (2005). Prevalence of endometritis and its effects on reproductive performance of dairy cows. Theriogenology 64, 1879–1888.
Prevalence of endometritis and its effects on reproductive performance of dairy cows.Crossref | GoogleScholarGoogle Scholar | 15961149PubMed |

Gong, X., Chen, Z., Liu, Y., Lu, Q., and Jin, Z. (2014). Gene expression profiling of the paracrine effects of uterine natural killer cells on human endometrial epithelial cells. Int. J. Endocrinol. 2014, 393707.
Gene expression profiling of the paracrine effects of uterine natural killer cells on human endometrial epithelial cells.Crossref | GoogleScholarGoogle Scholar | 24790599PubMed |

Hare, W. R., Hoyt, P. G., Hohn, C., and Higgins, J. A. (2008). Ribosomal RNA-based analysis of the bacterial flora from the conjunctivae of cattle with bovine keratoconjunctivitis (BKC). Vet. Microbiol. 131, 358–368.
Ribosomal RNA-based analysis of the bacterial flora from the conjunctivae of cattle with bovine keratoconjunctivitis (BKC).Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXhtVOisbrL&md5=ef05609c222349bc131eca8917182201CAS | 18513895PubMed |

Herath, S., Fischer, D. P., Werling, D., Williams, E. J., Lilly, S. T., Dobson, H., Bryant, C. E., and Sheldon, I. M. (2006). Expression and function of Toll-like receptor 4 in the endometrial cells of the uterus. Endocrinology 147, 562–570.
Expression and function of Toll-like receptor 4 in the endometrial cells of the uterus.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28XptFKq&md5=4c343a46af1fa65e774bb69d636f7e60CAS | 16223858PubMed |

Herath, S., Lilly, S. T., Santos, N. R., Gilbert, R. O., Goetze, L., Bryant, C. E., White, J. O., Cronin, J., and Sheldon, I. M. (2009a). Expression of genes associated with immunity in the endometrium of cattle with disparate postpartum uterine disease and fertility. Reprod. Biol. Endocrinol. 7, 55.
Expression of genes associated with immunity in the endometrium of cattle with disparate postpartum uterine disease and fertility.Crossref | GoogleScholarGoogle Scholar | 19476661PubMed |

Herath, S., Lilly, S. T., Fischer, D. P., Williams, E. J., Dobson, H., Bryant, C. E., and Sheldon, I. M. (2009b). Bacterial lipopolysaccharide induces an endocrine switch from prostaglandin F2 to prostaglandin E2 in bovine endometrium. Endocrinology 150, 1912–1920.
Bacterial lipopolysaccharide induces an endocrine switch from prostaglandin F2 to prostaglandin E2 in bovine endometrium.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXktVWlsLk%3D&md5=5b2d9f50ce80361e6b38fa2a893d0f69CAS | 19056817PubMed |

Huang, S. J., Schatz, F., Masch, R., Rahman, M., Buchwalder, L., Niven-Fairchild, T., Tang, C., Abrahams, V. M., Krikun, G., and Lockwood, C. J. (2006). Regulation of chemokine production in response to pro-inflammatory cytokines in first trimester decidual cells. J. Reprod. Immunol. 72, 60–73.
Regulation of chemokine production in response to pro-inflammatory cytokines in first trimester decidual cells.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28Xht1ShtLbI&md5=14c6b173586594c4f9dd3c2472e938c0CAS | 16806486PubMed |

Hussain, A. M., Daniel, R. C., and O’Boyle, D. (1990). Postpartum uterine flora following normal and abnormal puerperium in cows. Theriogenology 34, 291–302.
Postpartum uterine flora following normal and abnormal puerperium in cows.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BD283pvFKjsw%3D%3D&md5=e548d79a62b93ac4d4a2a9e16eb8f1a6CAS | 16726838PubMed |

Imakawa, K., Imai, M., Sakai, A., Suzuki, M., Nagaoka, K., Sakai, S., Lee, S.-R., Chang, K.-T., Echternkamp, S. E., and Christenson, R. K. (2006). Regulation of conceptus adhesion by endometrial CXC chemokines during the implantation period in sheep. Mol. Reprod. Dev. 73, 850–858.
Regulation of conceptus adhesion by endometrial CXC chemokines during the implantation period in sheep.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28XlsFahsr8%3D&md5=c5a0fd517258749bb545c05d4353e183CAS | 16596627PubMed |

Kasimanickam, R., Duffield, T. F., Foster, R. A., Gartley, C. J., Leslie, K. E., Walton, J. S., and Johnson, W. H. (2004). Endometrial cytology and ultrasonography for the detection of subclinical endometritis in postpartum dairy cows. Theriogenology 62, 9–23.
Endometrial cytology and ultrasonography for the detection of subclinical endometritis in postpartum dairy cows.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BD2c3mtFSkuw%3D%3D&md5=1ff03d40cc6e0157db43681d8323304cCAS | 15159097PubMed |

Kim, J. J., Quin, P. A., and Fortier, M. A. (1994). Ureaplasma diversum infection in vitro alters prostaglandin E2 and prostaglandin F2a production by bovine endometrial cells without affecting cell viability. Infect. Immun. 62, 1528–1533.
| 1:CAS:528:DyaK2cXksl2qsrY%3D&md5=866cbba55d06c9fc16b7d11f567f1f20CAS | 8168914PubMed |

Kitaya, K., and Yasuo, T. (2010). Aberrant expression of selectin E, CXCL1 and CXCL13 in chronic endometritis. Mod. Pathol. 23, 1136–1146.
Aberrant expression of selectin E, CXCL1 and CXCL13 in chronic endometritis.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXpsFeksrg%3D&md5=ffb8229715184bb6a7a6b71c05d69d07CAS | 20495539PubMed |

Konnai, S., Usui, T., Ohashi, K., and Onuma, M. (2003). The rapid quantitative analysis of bovine cytokine genes by real-time RT-PCR. Vet. Microbiol. 94, 283–294.
The rapid quantitative analysis of bovine cytokine genes by real-time RT-PCR.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3sXkvVCmtrw%3D&md5=dfc88426cedf6dd2c83ce548b010dfaeCAS | 12829382PubMed |

LeBlanc, S. J. (2012). Interactions of metabolism, inflammation and reproductive tract health in the postpartum period in dairy cattle. Reprod. Domest. Anim. 47, 18–30.
Interactions of metabolism, inflammation and reproductive tract health in the postpartum period in dairy cattle.Crossref | GoogleScholarGoogle Scholar | 22913557PubMed |

LeBlanc, S. J., Osawa, T., and Dubuc, J. (2011). Reproductive tract defence and disease in postpartum dairy cows. Theriogenology 76, 1610–1618.
Reproductive tract defence and disease in postpartum dairy cows.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXhsVanurzF&md5=0294ce315dfde1027b45cc340ca0badfCAS | 21890187PubMed |

Liu, M.-C., Wu, C.-M., Liu, Y.-C., Zhao, J.-C., Yang, Y.-L., and Shen, J.-Z. (2009). Identification, susceptibility, and detection of integron-gene cassettes of Arcanobacterium pyogenes in bovine endometritis. J. Dairy Sci. 92, 3659–3666.
Identification, susceptibility, and detection of integron-gene cassettes of Arcanobacterium pyogenes in bovine endometritis.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXptVWktbk%3D&md5=a9626d95c6a7612434bfc7bad5df8992CAS | 19620647PubMed |

Logan, N. A. (2012). Bacillus and relatives in foodborne illness. J. Appl. Microbiol. 112, 417–429.
Bacillus and relatives in foodborne illness.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38XkvVCjtrc%3D&md5=63a674efac4d459cda41184322bcfb97CAS | 22121830PubMed |

Logan, N. A., and De Vos, P. (2009) Bacillus. In ‘Bergey’s Manual of Systematic Bacteriology’. 2nd edn. (Eds P. De Vos, G. Garrity, D. Jones, N. R. Krieg, W. Ludwig, F. A. Rainey, K.-H. Schleifer and W. Whitman.) p. 48. (Springer: New York.)

Majewska, M., Woclawek-Potocka, I., Bah, M. M., Hapunik, J., Piotrowska, K. K., Tasaki, Y., Acosta, T. J., Okuda, K., and Skarzynski, D. J. (2010). Is interleukin-1alpha a luteotrophic or luteolytic agent in cattle? Reproduction 139, 665–672.
Is interleukin-1alpha a luteotrophic or luteolytic agent in cattle?Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXjtV2ltrg%3D&md5=7bd5c57c9beed040ecd62947ae984326CAS | 20032213PubMed |

Messier, S., Higgins, R., Couture, Y., and Morin, M. (1984). Comparison of swabbing and biopsy for studying the flora of the bovine uterus. Can. Vet. J. 25, 283–288.
| 1:STN:280:DC%2BC3crptlKitw%3D%3D&md5=30be290f3cb09c78e895d8bcb63bc507CAS | 17422427PubMed |

Miessen, K., Einspanier, R., and Schoen, J. (2012). Establishment and characterisation of a differentiated epithelial cell-culture model derived from the porcine cervix uteri. BMC Vet. Res. 8, 31.
Establishment and characterisation of a differentiated epithelial cell-culture model derived from the porcine cervix uteri.Crossref | GoogleScholarGoogle Scholar | 22429795PubMed |

Mokhtar, N. M., Cheng, C.-w., Cook, E., Bielby, H., Smith, S. K., and Charnock-Jones, D. S. (2010). Progestin regulates chemokine (C-X-C motif) ligand 14 transcript level in human endometrium. Mol. Hum. Reprod. 16, 170–177.
Progestin regulates chemokine (C-X-C motif) ligand 14 transcript level in human endometrium.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXhslKru74%3D&md5=b3052bc6968b2c8045c25f62e0eb9c60CAS | 19903701PubMed |

Nieminen, T., Rintaluoma, N., Andersson, M., Taimisto, A.-M., Ali-Vehmas, T., Seppälä, A., Priha, O., and Salkinoja-Salonen, M. (2007). Toxinogenic Bacillus pumilus and Bacillus licheniformis from mastitic milk. Vet. Microbiol. 124, 329–339.
Toxinogenic Bacillus pumilus and Bacillus licheniformis from mastitic milk.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXpsFGrsro%3D&md5=9530fedc451f55bf89494a86cd84cfc2CAS | 17611049PubMed |

Nomiyama, H., Osada, N., and Yoshie, O. (2010). The evolution of mammalian chemokine genes. Cytokine Growth Factor Rev. 21, 253–262.
The evolution of mammalian chemokine genes.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXhtFGjsbfM&md5=f72cba6df5ce9bb2edd53a3e67dd81faCAS | 20434943PubMed |

Odau, S., Gabler, C., Holder, C., and Einspanier, R. (2006). Differential expression of cyclooxygenase 1 and cyclooxygenase 2 in the bovine oviduct. J. Endocrinol. 191, 263–274.
Differential expression of cyclooxygenase 1 and cyclooxygenase 2 in the bovine oviduct.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28Xht1eju7fM&md5=38696410edc9ffe63852b64a4887c1f9CAS | 17065409PubMed |

Panangala, V. S., Fish, N. A., and Barnum, D. A. (1978). Microflora of the cervico–vaginal mucus of repeat-breeder cows. Can. Vet. J. 19, 83–89.
| 1:STN:280:DyaE1c7ovVKitQ%3D%3D&md5=2624a52be7ce12e91900feb0c389c3b2CAS | 657078PubMed |

Rafii, F., Williams, A. J., Park, M., Sims, L. M., Heinze, T. M., Cerniglia, C. E., and Sutherland, J. B. (2009). Isolation of bacterial strains from bovine fecal microflora capable of degradation of ceftiofur. Vet. Microbiol. 139, 89–96.
Isolation of bacterial strains from bovine fecal microflora capable of degradation of ceftiofur.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXhtFynsbfP&md5=ca5a5cf14c326d032c4e9234620e8a43CAS | 19428193PubMed |

Reutershan, J., and Ley, K. (2004). Bench-to-bedside review: acute respiratory distress syndrome – how neutrophils migrate into the lung. Crit. Care 8, 453–461.
Bench-to-bedside review: acute respiratory distress syndrome – how neutrophils migrate into the lung.Crossref | GoogleScholarGoogle Scholar | 15566616PubMed |

Santos, T. M., and Bicalho, R. C. (2012). Diversity and succession of bacterial communities in the uterine fluid of postpartum metritic, endometritic and healthy dairy cows. PLoS ONE 7, e53048.
Diversity and succession of bacterial communities in the uterine fluid of postpartum metritic, endometritic and healthy dairy cows.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3sXotVahsw%3D%3D&md5=2f0ee2f81c2e3d87f3334f9eab1dac3eCAS | 23300859PubMed |

Santos, T. M., Gilbert, R. O., and Bicalho, R. C. (2011). Metagenomic analysis of the uterine bacterial microbiota in healthy and metritic postpartum dairy cows. J. Dairy Sci. 94, 291–302.
Metagenomic analysis of the uterine bacterial microbiota in healthy and metritic postpartum dairy cows.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXjslCntLc%3D&md5=3214dcda4b2e3d2cbfbf5d2b74b2ef5aCAS | 21183039PubMed |

Sens, A., and Heuwieser, W. (2013). Presence of Escherichia coli, Trueperella pyogenes, α-hemolytic streptococci and coagulase-negative staphylococci and prevalence of subclinical endometritis. J. Dairy Sci. 96, 6347–6354.
Presence of Escherichia coli, Trueperella pyogenes, α-hemolytic streptococci and coagulase-negative staphylococci and prevalence of subclinical endometritis.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3sXht1WnsrzP&md5=7b67e715906f1e33b4efdd3e30bc30f0CAS | 23910551PubMed |

Sentman, C. L., Meadows, S. K., Wira, C. R., and Eriksson, M. (2004). Recruitment of uterine NK cells: induction of CXC chemokine ligands 10 and 11 in human endometrium by oestradiol and progesterone. J. Immunol. 173, 6760–6766.
Recruitment of uterine NK cells: induction of CXC chemokine ligands 10 and 11 in human endometrium by oestradiol and progesterone.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2cXhtVShsb%2FI&md5=2d3d83a31f34cbb69a28ce9aa5abcc92CAS | 15557169PubMed |

Sheldon, I. M., and Roberts, M. H. (2010). Toll-like receptor 4 mediates the response of epithelial and stromal cells to lipopolysaccharide in the endometrium. PLoS ONE 5, e12906.
Toll-like receptor 4 mediates the response of epithelial and stromal cells to lipopolysaccharide in the endometrium.Crossref | GoogleScholarGoogle Scholar | 20877575PubMed |

Sheldon, I. M., Lewis, G. S., LeBlanc, S., and Gilbert, R. O. (2006). Defining postpartum uterine disease in cattle. Theriogenology 65, 1516–1530.
Defining postpartum uterine disease in cattle.Crossref | GoogleScholarGoogle Scholar | 16226305PubMed |

Sheldon, I. M., Cronin, J., Goetze, L., Donofrio, G., and Schuberth, H.-J. (2009a). Defining postpartum uterine disease and the mechanisms of infection and immunity in the female reproductive tract in cattle. Biol. Reprod. 81, 1025–1032.
Defining postpartum uterine disease and the mechanisms of infection and immunity in the female reproductive tract in cattle.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXhsV2lt7vP&md5=bd65dca74aab98b105d9c06b7ec4e447CAS | 19439727PubMed |

Sheldon, I. M., Price, S. B., Cronin, J., Gilbert, R. O., and Gadsby, J. E. (2009b). Mechanisms of infertility associated with clinical and subclinical endometritis in high-producing dairy cattle. Reprod. Domest. Anim. 44, 1–9.
Mechanisms of infertility associated with clinical and subclinical endometritis in high-producing dairy cattle.Crossref | GoogleScholarGoogle Scholar | 19660075PubMed |

Sheldon, I. M., Rycroft, A. N., Dogan, B., Craven, M., Bromfield, J. J., Chandler, A., Roberts, M. H., Price, S. B., Gilbert, R. O., Simpson, K. W., and Sturtevant, J. (2010). Specific strains of Escherichia coli are pathogenic for the endometrium of cattle and cause pelvic inflammatory disease in cattle and mice. PLoS ONE 5, e9192.
Specific strains of Escherichia coli are pathogenic for the endometrium of cattle and cause pelvic inflammatory disease in cattle and mice.Crossref | GoogleScholarGoogle Scholar | 20169203PubMed |

Sheldon, I. M., Cronin, J. G., Healey, G. D., Gabler, C., Heuwieser, W., Streyl, D., Bromfield, J., Miyamoto, A., Fergani, C., and Dobson, H. (2014). Innate immunity and inflammation of the bovine female reproductive tract in health and disease. Reproduction 148, R41–R51.
Innate immunity and inflammation of the bovine female reproductive tract in health and disease.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2cXhsVert7bM&md5=4943eda179146a08d4ec44a433155e27CAS | 24890752PubMed |

Silva, A. P., Costa, E. A., Macêdo, A. A., Martins, T. da M., Borges, A. M., Paixão, T. A., and Santos, R. L. (2012). Transcription of pattern recognition receptors and abortive agents induced chemokines in the bovine pregnant uterus. Vet. Immunol. Immunopathol. 145, 248–256.
Transcription of pattern recognition receptors and abortive agents induced chemokines in the bovine pregnant uterus.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38XitVertb0%3D&md5=46b807b5e277316bf46d69d3aa41f199CAS | 22153993PubMed |

Singh, J., Murray, R. D., Mshelia, G., and Woldehiwet, Z. (2008). The immune status of the bovine uterus during the peripartum period. Vet. J. 175, 301–309.
The immune status of the bovine uterus during the peripartum period.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXjtlOqurk%3D&md5=8aef405ff45e98b24e406a119e396178CAS | 17400489PubMed |

Suominen, I., Andersson, M. A., Andersson, M. C., Hallaksela, A. M., Kämpfer, P., Rainey, F. A., and Salkinoja-Salonen, M. (2001). Toxic Bacillus pumilus from indoor air, recycled paper pulp, Norway spruce, food poisoning outbreaks and clinical samples. Syst. Appl. Microbiol. 24, 267–276.
Toxic Bacillus pumilus from indoor air, recycled paper pulp, Norway spruce, food poisoning outbreaks and clinical samples.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3MXmsl2it7k%3D&md5=b1f96192fa5ecdf58911f896b8bf6c3fCAS | 11518331PubMed |

Tanikawa, M., Acosta, T. J., Fukui, T., Murakami, S., Korzekwa, A., Skarzynski, D. J., Piotrowska, K. K., Park, C. K., and Okuda, K. (2005). Regulation of prostaglandin synthesis by interleukin-1alpha in bovine endometrium during the oestrous cycle. Prostaglandins Other Lipid Mediat. 78, 279–290.
Regulation of prostaglandin synthesis by interleukin-1alpha in bovine endometrium during the oestrous cycle.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXht1GntbrK&md5=d299d71e034dd14a2335ae9b128e97b1CAS | 16303622PubMed |

Turner, M. L., Cronin, J. G., Healey, G. D., and Sheldon, I. M. (2014). Epithelial and stromal cells of bovine endometrium have roles in innate immunity and initiate inflammatory responses to bacterial lipopeptides in vitro via Toll-like receptors TLR2, TLR1 and TLR6. Endocrinology 155, 1453–1465.
Epithelial and stromal cells of bovine endometrium have roles in innate immunity and initiate inflammatory responses to bacterial lipopeptides in vitro via Toll-like receptors TLR2, TLR1 and TLR6.Crossref | GoogleScholarGoogle Scholar | 24437488PubMed |

Vandesompele, J., Preter, K. de, Pattyn, F., Poppe, B., van Roy, N., Paepe, A. de, and Speleman, F. (2002). Accurate normalisation of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biol. 3, research0034–research0034.11.
Accurate normalisation of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes.Crossref | GoogleScholarGoogle Scholar | 12184808PubMed |

Wagener, K., Drillich, M., Baumgardt, S., Kampfer, P., Busse, H.-J., and Ehling-Schulz, M. (2014). Falsiporphyromonas endometrii gen. nov., sp. nov., isolated from the post-partum bovine uterus, and emended description of the genus Porphyromonas Shah and Collins 1988. Int. J. Syst. Evol. Microbiol. 64, 642–649.
Falsiporphyromonas endometrii gen. nov., sp. nov., isolated from the post-partum bovine uterus, and emended description of the genus Porphyromonas Shah and Collins 1988.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2cXhtlClsrrL&md5=234f76390b5dfb3d1a65ff1bb89b7e0fCAS | 24158948PubMed |

Walker, C. G., Meier, S., Mitchell, M. D., Roche, J. R., and Littlejohn, M. (2009). Evaluation of real-time PCR endogenous control genes for analysis of gene expression in bovine endometrium. BMC Mol. Biol. 10, 100.
Evaluation of real-time PCR endogenous control genes for analysis of gene expression in bovine endometrium.Crossref | GoogleScholarGoogle Scholar | 19878604PubMed |

Weisburg, W. G., Barns, S. M., Pelletier, D. A., and Lane, D. J. (1991). 16S ribosomal DNA amplification for phylogenetic study. J. Bacteriol. 173, 697–703.
| 1:CAS:528:DyaK3MXhsl2lurY%3D&md5=0d1a6455611a9e9b3552c893d4b69a13CAS | 1987160PubMed |

Westermann, S., Drillich, M., Kaufmann, T. B., Madoz, L. V., and Heuwieser, W. (2010). A clinical approach to determine false positive findings of clinical endometritis by vaginoscopy by the use of uterine bacteriology and cytology in dairy cows. Theriogenology 74, 1248–1255.
A clinical approach to determine false positive findings of clinical endometritis by vaginoscopy by the use of uterine bacteriology and cytology in dairy cows.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BC3cfjvV2htg%3D%3D&md5=6ceee752f810cc9a119eab5ef38438c5CAS | 20615532PubMed |

Williams, E. J., Fischer, D. P., Noakes, D. E., England, G. C. W., Rycroft, A., Dobson, H., and Sheldon, I. M. (2007). The relationship between uterine pathogen growth density and ovarian function in the postpartum dairy cow. Theriogenology 68, 549–559.
The relationship between uterine pathogen growth density and ovarian function in the postpartum dairy cow.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXotlWqu7w%3D&md5=636e0a5789176125a88c2d5a357f1fd1CAS | 17574659PubMed |

Zerbe, H., Schuberth, H.-J., Engelke, F., Frank, J., Klug, E., and Leibold, W. (2003). Development and comparison of in vivo and in vitro models for endometritis in cows and mares. Theriogenology 60, 209–223.
Development and comparison of in vivo and in vitro models for endometritis in cows and mares.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BD3szhtVejsw%3D%3D&md5=20e273c459e56079bf55150c8d0cc607CAS | 12749935PubMed |