Tolerance and Innate Immunity Shape the Development of Postpartum Uterine Disease and the Impact of Endometritis in Dairy Cattle

Literature Cited

1. 1.  Sheldon IM, Cronin J, Goetze L, Donofrio G, Schuberth HJ 2009. Defining postpartum uterine disease and the mechanisms of infection and immunity in the female reproductive tract in cattle. Biol. Reprod. 81:1025–32
   [Google Scholar]
2. 2.  Britt JH, Cushman RA, Dechow CD, Dobson H, Humblot P et al. 2018. Invited review: learning from the future: a vision for dairy farms and cows in 2067. J. Dairy Sci. 101:3722–41
   [Google Scholar]
3. 3.  Raberg L, Sim D, Read AF 2007. Disentangling genetic variation for resistance and tolerance to infectious diseases in animals. Science 318:812–14Provides a framework for exploring resistance and tolerance in animals.
   [Google Scholar]
4. 4.  Schneider DS, Ayres JS 2008. Two ways to survive infection: what resistance and tolerance can teach us about treating infectious diseases. Nat. Rev. Immunol. 8:889–95
   [Google Scholar]
5. 5.  Medzhitov R, Schneider DS, Soares MP 2012. Disease tolerance as a defense strategy. Science 335:936–41
   [Google Scholar]
6. 6.  Read AF, Graham AL, Raberg L 2008. Animal defenses against infectious agents: Is damage control more important than pathogen control?. PLOS Biol 6:e1000004
   [Google Scholar]
7. 7.  Sheldon IM, Noakes DE, Rycroft AN, Pfeiffer DU, Dobson H 2002. Influence of uterine bacterial contamination after parturition on ovarian dominant follicle selection and follicle growth and function in cattle. Reproduction 123:837–45Evidence for how postpartum uterine disease affects uterine health and ovarian follicle growth and development in vivo.
   [Google Scholar]
8. 8.  Gier HT, Marion GB 1968. Uterus of the cow after parturition: involutional changes. Am. J. Vet. Res. 29:83–96
   [Google Scholar]
9. 9.  Sheldon IM, Noakes DE, Rycroft AN, Dobson H 2003. The effect of intrauterine administration of estradiol on postpartum uterine involution in cattle. Theriogenology 59:1357–71
   [Google Scholar]
10. 10.  Wagner WC, Hansel W 1969. Reproductive physiology of the post partum cow. l. Clinical histological findings. J. Reprod. Fertil. 18:493–500
    [Google Scholar]
11. 11.  Beam SW, Butler WR 1997. Energy balance and ovarian follicle development prior to the first ovulation postpartum in dairy cows receiving three levels of dietary fat. Biol. Reprod. 56:133–42
    [Google Scholar]
12. 12.  Crowe MA 2008. Resumption of ovarian cyclicity in post-partum beef and dairy cows. Reprod. Domest. Anim. 43:Suppl. 520–28
    [Google Scholar]
13. 13.  Cheong SH, Sa Filho OG, Absalon-Medina VA, Pelton SH, Butler WR, Gilbert RO 2016. Metabolic and endocrine differences between dairy cows that do or do not ovulate first postpartum dominant follicles. Biol. Reprod. 94:18
    [Google Scholar]
14. 14.  Peter AT, Bosu WT, DeDecker RJ 1989. Suppression of preovulatory luteinizing hormone surges in heifers after intrauterine infusions of Escherichia coli endotoxin. Am. J. Vet. Res. 50:368–73
    [Google Scholar]
15. 15.  Karstrup CC, Klitgaard K, Jensen TK, Agerholm JS, Pedersen HG 2017. Presence of bacteria in the endometrium and placentomes of pregnant cows. Theriogenology 99:43–47Visualization of bacteria in the endometrium of animals during pregnancy showing that the uterus is not sterile.
    [Google Scholar]
16. 16.  Moore SG, Ericsson AC, Poock SE, Melendez P, Lucy MC 2017. Hot topic: 16S rRNA gene sequencing reveals the microbiome of the virgin and pregnant bovine uterus. J. Dairy Sci. 100:4953–60
    [Google Scholar]
17. 17.  Huszenicza G, Fodor M, Gacs M, Kulcsar M, Dohmen MJW et al. 1991. Uterine bacteriology, resumption of cyclic ovarian activity and fertility in postpartum cows kept in large-scale dairy herds. Reprod. Domest. Anim. 34:237–45
    [Google Scholar]
18. 18.  Machado VS, Oikonomou G, Bicalho ML, Knauer WA, Gilbert R, Bicalho RC 2012. Investigation of postpartum dairy cows’ uterine microbial diversity using metagenomic pyrosequencing of the 16S rRNA gene. Vet. Microbiol. 159:460–69
    [Google Scholar]
19. 19.  Santos TM, Bicalho RC 2012. Diversity and succession of bacterial communities in the uterine fluid of postpartum metritic, endometritic and healthy dairy cows. PLOS ONE 7:e53048
    [Google Scholar]
20. 20.  Peng Y, Wang Y, Hang S, Zhu W 2013. Microbial diversity in uterus of healthy and metritic postpartum Holstein dairy cows. Folia Microbiol 58:593–600
    [Google Scholar]
21. 21.  Wagener K, Prunner I, Pothmann H, Drillich M, Ehling-Schulz M 2015. Diversity and health status specific fluctuations of intrauterine microbial communities in postpartum dairy cows. Vet. Microbiol. 175:286–93
    [Google Scholar]
22. 22.  Knudsen LR, Karstrup CC, Pedersen HG, Agerholm JS, Jensen TK, Klitgaard K 2015. Revisiting bovine pyometra: new insights into the disease using a culture-independent deep sequencing approach. Vet. Microbiol. 175:319–24
    [Google Scholar]
23. 23.  Olson JD, Ball L, Mortimer RG, Farin PW, Adney WS, Huffman EM 1984. Aspects of bacteriology and endocrinology of cows with pyometra and retained fetal membranes. Am. J. Vet. Res. 45:2251–55
    [Google Scholar]
24. 24.  Ruder CA, Sasser RG, Williams RJ, Ely JK, Bull RC, Butler JE 1981. Uterine infections in the postpartum cow: II. Possible synergistic effect of Fusobacteriumnecrophorum and Corynebacteriumpyogenes. . Theriogenology 15:573–80
    [Google Scholar]
25. 25.  Sheldon IM, Rycroft AN, Dogan B, Craven M, Bromfield JJ et al. 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
    [Google Scholar]
26. 26.  Bicalho RC, Machado VS, Bicalho ML, Gilbert RO, Teixeira AG et al. 2010. Molecular and epidemiological characterization of bovine intrauterine Escherichia coli. J. . Dairy Sci 93:5818–30
    [Google Scholar]
27. 27.  Moresco EM, LaVine D, Beutler B 2011. Toll-like receptors. Curr. Biol. 21:R488–93
    [Google Scholar]
28. 28.  Bonnett BN, Martin SW, Gannon VP, Miller RB, Etherington WG 1991. Endometrial biopsy in Holstein-Friesian dairy cows. III. Bacteriological analysis and correlations with histological findings. Can. J. Vet. Res. 55:168–73
    [Google Scholar]
29. 29.  Westermann S, Drillich M, Kaufmann TB, Madoz LV, 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 74:1248–55
    [Google Scholar]
30. 30.  Gilbert RO, Santos NR 2016. Dynamics of postpartum endometrial cytology and bacteriology and their relationship to fertility in dairy cows. Theriogenology 85:1367–74
    [Google Scholar]
31. 31.  Amos MR, Healey GD, Goldstone RJ, Mahan S, Duvel A et al. 2014. Differential endometrial cell sensitivity to a cholesterol-dependent cytolysin links Trueperellapyogenes to uterine disease in cattle. Biol. Reprod. 90:54Dissection of the role of pyolysin in the bovine endometrium and identifying the sensitivity of stromal cells to pyolysin.
    [Google Scholar]
32. 32.  Preta G, Lotti V, Cronin JG, Sheldon IM 2015. Protective role of the dynamin inhibitor Dynasore against the cholesterol-dependent cytolysin of Trueperellapyogenes. . FASEB J 29:1516–28
    [Google Scholar]
33. 33.  Ayliffe TR, Noakes DE 1982. Effects of exogenous oestrogen and experimentally induced endometritis on absorption of sodium benzylpenicillin from the cow's uterus. Vet. Rec. 110:96–98
    [Google Scholar]
34. 34.  Lin HK, Oltenacu PA, Van Vleck LD, Erb HN, Smith RD 1989. Heritabilities of and genetic correlations among six health problems in Holstein cows. J. Dairy Sci. 72:180–86
    [Google Scholar]
35. 35.  Zwald NR, Weigel KA, Chang YM, Welper RD, Clay JS 2004. Genetic selection for health traits using producer-recorded data. I. Incidence rates, heritability estimates, and sire breeding values. J. Dairy Sci. 87:4287–94
    [Google Scholar]
36. 36.  Pinedo PJ, Galvao KN, Seabury CM 2013. Innate immune gene variation and differential susceptibility to uterine diseases in Holstein cows. Theriogenology 80:384–90
    [Google Scholar]
37. 37.  Markusfeld O 1984. Factors responsible for post parturient metritis in dairy cattle. Vet. Rec. 114:539–42
    [Google Scholar]
38. 38.  Huzzey JM, Veira DM, Weary DM, von Keyserlingk MA 2007. Prepartum behavior and dry matter intake identify dairy cows at risk for metritis. J. Dairy Sci. 90:3220–33
    [Google Scholar]
39. 39.  Dubuc J, Duffield TF, Leslie KE, Walton JS, LeBlanc SJ 2010. Risk factors for postpartum uterine diseases in dairy cows. J. Dairy Sci. 93:5764–71
    [Google Scholar]
40. 40.  Potter T, Guitian J, Fishwick J, Gordon PJ, Sheldon IM 2010. Risk factors for clinical endometritis in postpartum dairy cattle. Theriogenology 74:127–34
    [Google Scholar]
41. 41.  Wathes DC, Cheng Z, Fenwick MA, Fitzpatrick R, Patton J 2011. Influence of energy balance on the somatotrophic axis and matrix metalloproteinase expression in the endometrium of the postpartum dairy cow. Reproduction 141:269–81
    [Google Scholar]
42. 42.  Chagas LM, Bass JJ, Blache D, Burke CR, Kay JK et al. 2007. Invited review: new perspectives on the roles of nutrition and metabolic priorities in the subfertility of high-producing dairy cows. J. Dairy Sci. 90:4022–32
    [Google Scholar]
43. 43.  Doepel L, Lessard M, Gagnon N, Lobley GE, Bernier JF et al. 2006. Effect of postruminal glutamine supplementation on immune response and milk production in dairy cows. J. Dairy Sci. 89:3107–21
    [Google Scholar]
44. 44.  Cai TQ, Weston PG, Lund LA, Brodie B, McKenna DJ, Wagner WC 1994. Association between neutrophil functions and periparturient disorders in cows. Am. J. Vet. Res. 55:934–43
    [Google Scholar]
45. 45.  Hammon DS, Evjen IM, Dhiman TR, Goff JP, Walters JL 2006. Neutrophil function and energy status in Holstein cows with uterine health disorders. Vet. Immunol. Immunopathol. 113:21–29
    [Google Scholar]
46. 46.  Galvao KN, Flaminio MJ, Brittin SB, Sper R, Fraga M et al. 2010. Association between uterine disease and indicators of neutrophil and systemic energy status in lactating Holstein cows. J. Dairy Sci. 93:2926–37
    [Google Scholar]
47. 47.  Turner ML, Cronin JG, Noleto PG, Sheldon IM 2016. Glucose availability and AMP-activated protein kinase link energy metabolism and innate immunity in the bovine endometrium. PLOS ONE 11:e0151416
    [Google Scholar]
48. 48.  Noleto PG, Saut JP, Sheldon IM 2017. Short communication: Glutamine modulates inflammatory responses to lipopolysaccharide in ex vivo bovine endometrium. J. Dairy Sci. 100:2207–12
    [Google Scholar]
49. 49.  Wathes DC 2012. Mechanisms linking metabolic status and disease with reproductive outcome in the dairy cow. Reprod. Domest. Anim. 47:Suppl. 4304–12
    [Google Scholar]
50. 50.  Sordillo LM, Contreras GA, Aitken SL 2009. Metabolic factors affecting the inflammatory response of periparturient dairy cows. Anim. Health Res. Rev. 10:53–63
    [Google Scholar]
51. 51.  O'Neill LA, Kishton RJ, Rathmell J 2016. A guide to immunometabolism for immunologists. Nat. Rev. Immunol. 16:553–65
    [Google Scholar]
52. 52.  Noakes DE, Wallace L, Smith GR 1991. Bacterial flora of the uterus of cows after calving on two hygienically contrasting farms. Vet. Rec. 128:440–42
    [Google Scholar]
53. 53.  Sheldon IM, Lewis GS, LeBlanc S, Gilbert RO 2006. Defining postpartum uterine disease in cattle. Theriogenology 65:1516–30Sets out the definitions and methods for scoring postpartum uterine disease.
    [Google Scholar]
54. 54.  de Boer MW, LeBlanc SJ, Dubuc J, Meier S, Heuwieser W et al. 2014. Invited review: systematic review of diagnostic tests for reproductive-tract infection and inflammation in dairy cows. J. Dairy Sci. 97:3983–99
    [Google Scholar]
55. 55.  Stojkov J, von Keyserlingk MA, Marchant-Forde JN, Weary DM 2015. Assessment of visceral pain associated with metritis in dairy cows. J. Dairy Sci. 98:5352–61
    [Google Scholar]
56. 56.  Fourichon C, Seegers H, Malher X 2000. Effect of disease on reproduction in the dairy cow: a meta-analysis. Theriogenology 53:1729–59
    [Google Scholar]
57. 57.  Haimerl P, Heuwieser W 2014. Invited review: antibiotic treatment of metritis in dairy cows: a systematic approach. J. Dairy Sci. 97:6649–61
    [Google Scholar]
58. 58.  Sheldon IM, Noakes DE 1998. Comparison of three treatments for bovine endometritis. Vet. Rec. 142:575–79
    [Google Scholar]
59. 59.  Sannmann I, Heuwieser W 2015. Technical note: intraobserver, interobserver, and test-retest reliabilities of an assessment of vaginal discharge from cows with and without acute puerperal metritis. J. Dairy Sci. 98:5460–66
    [Google Scholar]
60. 60.  Denis-Robichaud J, Dubuc J 2015. Determination of optimal diagnostic criteria for purulent vaginal discharge and cytological endometritis in dairy cows. J. Dairy Sci. 98:6848–55
    [Google Scholar]
61. 61.  LeBlanc SJ, Duffield TF, Leslie KE, Bateman KG, Keefe GP et al. 2002. Defining and diagnosing postpartum clinical endometritis and its impact on reproductive performance in dairy cows. J. Dairy Sci. 85:2223–36
    [Google Scholar]
62. 62.  Gernand E, Rehbein P, von Borstel UU, König S 2012. Incidences of and genetic parameters for mastitis, claw disorders, and common health traits recorded in dairy cattle contract herds. J. Dairy Sci. 95:2144–56
    [Google Scholar]
63. 63.  Borsberry S, Dobson H 1989. Periparturient diseases and their effect on reproductive performance in five dairy herds. Vet. Rec. 124:217–19
    [Google Scholar]
64. 64.  LeBlanc SJ, Duffield TF, Leslie KE, Bateman KG, Keefe GP et al. 2002. The effect of treatment of clinical endometritis on reproductive performance in dairy cows. J. Dairy Sci. 85:2237–49
    [Google Scholar]
65. 65.  Steffan J, Adriamanga S, Thibier M 1984. Treatment of metritis with antibiotics or prostaglandin F_2a and influence of ovarian cyclicity in dairy cows. Am. J. Vet. Res. 45:1090–94
    [Google Scholar]
66. 66.  Griffin JFT, Hartigan PJ, Nunn WR 1974. Non-specific uterine infection and bovine fertility. I. Infection patterns and endometritis during the first seven weeks post-partum. Theriogenology 1:91–106
    [Google Scholar]
67. 67.  Kasimanickam R, Duffield TF, Foster RA, Gartley CJ, Leslie KE et al. 2004. Endometrial cytology and ultrasonography for the detection of subclinical endometritis in postpartum dairy cows. Theriogenology 62:9–23Recognition of the importance of subclinical endometritis in cattle.
    [Google Scholar]
68. 68.  Gilbert RO, Shin ST, Guard CL, Erb HN, Frajblat M 2005. Prevalence of endometritis and its effects on reproductive performance of dairy cows. Theriogenology 64:1879–88
    [Google Scholar]
69. 69.  Lima FS, Vieira-Neto A, Vasconcellos GS, Mingoti RD, Karakaya E et al. 2014. Efficacy of ampicillin trihydrate or ceftiofur hydrochloride for treatment of metritis and subsequent fertility in dairy cows. J. Dairy Sci. 97:5401–14
    [Google Scholar]
70. 70.  Fischer C, Drillich M, Odau S, Heuwieser W, Einspanier R, 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. 22:818–29
    [Google Scholar]
71. 71.  Ghasemi F, Gonzalez-Cano P, Griebel PJ, Palmer C 2012. Proinflammatory cytokine gene expression in endometrial cytobrush samples harvested from cows with and without subclinical endometritis. Theriogenology 78:1538–47
    [Google Scholar]
72. 72.  Gabler C, Drillich M, Fischer C, Holder C, Heuwieser W, Einspanier R 2009. Endometrial expression of selected transcripts involved in prostaglandin synthesis in cows with endometritis. Theriogenology 71:993–1004
    [Google Scholar]
73. 73.  Gabler C, Fischer C, Drillich M, Einspanier R, Heuwieser W 2010. Time-dependent mRNA expression of selected pro-inflammatory factors in the endometrium of primiparous cows postpartum. Reprod. Biol. Endocrinol. 8:152
    [Google Scholar]
74. 74.  Kasimanickam R, Kasimanickam V, Kastelic JP 2014. Mucin 1 and cytokines mRNA in endometrium of dairy cows with postpartum uterine disease or repeat breeding. Theriogenology 81:952–58
    [Google Scholar]
75. 75.  Wagener K, Gabler C, Drillich M 2017. A review of the ongoing discussion about definition, diagnosis and pathomechanism of subclinical endometritis in dairy cows. Theriogenology 94:21–30
    [Google Scholar]
76. 76.  Bogado Pascottini O, Hostens M, Dini P, Vandepitte J, Ducatelle R, Opsomer G 2016. Comparison between cytology and histopathology to evaluate subclinical endometritis in dairy cows. Theriogenology 86:1550–56
    [Google Scholar]
77. 77.  Serhan CN, Chiang N, Van Dyke TE 2008. Resolving inflammation: dual anti-inflammatory and pro-resolution lipid mediators. Nat. Rev. Immunol. 8:349–61
    [Google Scholar]
78. 78.  Kotas ME, Medzhitov R 2015. Homeostasis, inflammation, and disease susceptibility. Cell 160:816–27
    [Google Scholar]
79. 79.  Kerestes M, Faigl V, Kulcsar M, Balogh O, Foldi J et al. 2009. Periparturient insulin secretion and whole-body insulin responsiveness in dairy cows showing various forms of ketone pattern with or without puerperal metritis. Domest. Anim. Endocrinol. 37:250–61
    [Google Scholar]
80. 80.  LeBlanc SJ 2012. Interactions of metabolism, inflammation, and reproductive tract health in the postpartum period in dairy cattle. Reprod. Domest. Anim. 47:Suppl. 518–30
    [Google Scholar]
81. 81.  Ravel J, Gajer P, Abdo Z, Schneider GM, Koenig SSK et al. 2011. Vaginal microbiome of reproductive-age women. PNAS 108:Suppl. 14680–87
    [Google Scholar]
82. 82.  Miller E, Beasley D, Dunn R, Archie E 2016. Lactobacilli dominance and vaginal pH: Why is the human vaginal microbiome unique?. Front. Microbiol. 7:1936
    [Google Scholar]
83. 83.  Deng Q, Odhiambo JF, Farooq U, Lam T, Dunn SM, Ametaj BN 2014. Intravaginal lactic acid bacteria modulated local and systemic immune responses and lowered the incidence of uterine infections in periparturient dairy cows. PLOS ONE 10:e0124167
    [Google Scholar]
84. 84.  Davies D, Meade KG, Herath S, Eckersall PD, Gonzalez D et al. 2008. Toll-like receptor and antimicrobial peptide expression in the bovine endometrium. Reprod. Biol. Endocrinol. 6:53
    [Google Scholar]
85. 85.  Hoelker M, Salilew-Wondim D, Drillich M, Christine GB, Ghanem N et al. 2012. Transcriptional response of the bovine endometrium and embryo to endometrial polymorphonuclear neutrophil infiltration as an indicator of subclinical inflammation of the uterine environment. Reprod. Fertil. Dev. 24:778–93
    [Google Scholar]
86. 86.  Chapwanya A, Meade KG, Doherty ML, Callanan JJ, Mee JF, O'Farrelly C 2009. Histopathological and molecular evaluation of Holstein-Friesian cows postpartum: toward an improved understanding of uterine innate immunity. Theriogenology 71:1396–407
    [Google Scholar]
87. 87.  Goldstein JL, Brown MS 1990. Regulation of the mevalonate pathway. Nature 343:425–30
    [Google Scholar]
88. 88.  Lange Y, Swaisgood MH, Ramos BV, Steck TL 1989. Plasma membranes contain half the phospholipid and 90% of the cholesterol and sphingomyelin in cultured human fibroblasts. J. Biol. Chem. 264:3786–93
    [Google Scholar]
89. 89.  Griffin S, Preta G, Sheldon IM 2017. Inhibiting mevalonate pathway enzymes increases stromal cell resilience to a cholesterol-dependent cytolysin. Sci. Rep. 7:17050
    [Google Scholar]
90. 90.  Griffin S, Healey GD, Sheldon IM 2018. Isoprenoids increase bovine endometrial stromal cell tolerance to the cholesterol-dependent cytolysin from Trueperellapyogenes. Biol. Reprod 99:749–60
91. 91.  Healey GD, Collier C, Griffin S, Schuberth HJ, Sandra O et al. 2016. Mevalonate biosynthesis intermediates are key regulators of innate immunity in bovine endometritis. J. Immunol. 196:823–31
    [Google Scholar]
92. 92.  Wathes DC, Cheng Z, Chowdhury W, Fenwick MA, Fitzpatrick R et al. 2009. Negative energy balance alters global gene expression and immune responses in the uterus of postpartum dairy cows. Physiol. Genom. 39:1–13
    [Google Scholar]
93. 93.  Hashizume K, Takahashi T, Shimizu M, Todoroki J, Shimada A et al. 2003. Matrix-metalloproteinases-2 and -9 production in bovine endometrial cell culture. J. Reprod. Dev. 49:45–53
    [Google Scholar]
94. 94.  Baxt LA, Garza-Mayers AC, Goldberg MB 2013. Bacterial subversion of host innate immune pathways. Science 340:697–701
    [Google Scholar]
95. 95.  Takeuchi O, Akira S 2010. Pattern recognition receptors and inflammation. Cell 140:805–20
    [Google Scholar]
96. 96.  Galvao KN, Santos NR, Galvao JS, Gilbert RO 2011. Association between endometritis and endometrial cytokine expression in postpartum Holstein cows. Theriogenology 76:290–99
    [Google Scholar]
97. 97.  Herath S, Lilly ST, Santos NR, Gilbert RO, Goetze L et al. 2009. Expression of genes associated with immunity in the endometrium of cattle with disparate postpartum uterine disease and fertility. Reprod. Biol. Endocrinol. 7:55
    [Google Scholar]
98. 98.  Healy LL, Cronin JG, Sheldon IM 2014. Endometrial cells sense and react to tissue damage during infection of the bovine endometrium via interleukin 1. Sci. Rep. 4:7060
    [Google Scholar]
99. 99.  Kim IH, Kang HG, Jeong JK, Hur TY, Jung YH 2014. Inflammatory cytokine concentrations in uterine flush and serum samples from dairy cows with clinical or subclinical endometritis. Theriogenology 82:427–32
    [Google Scholar]
100. 100.  Baumann H, Gauldie J 1994. The acute phase response. Immunol. Today 15:74–80
     [Google Scholar]
101. 101.  Smith BI, Donovan GA, Risco CA, Young CR, Stanker LH 1998. Serum haptoglobin concentrations in Holstein dairy cattle with toxic puerperal metritis. Vet. Rec. 142:83–85
     [Google Scholar]
102. 102.  Sheldon IM, Noakes DE, Rycroft A, Dobson H 2001. Acute phase protein response to postpartum uterine bacterial contamination in cattle. Vet. Rec. 148:172–75
     [Google Scholar]
103. 103.  Lecchi C, Dilda F, Sartorelli P, Ceciliani F 2012. Widespread expression of SAA and Hp RNA in bovine tissues after evaluation of suitable reference genes. Vet. Immunol. Immunopathol. 145:556–62
     [Google Scholar]
104. 104.  Swangchan-Uthai T, Chen Q, Kirton SE, Fenwick MA, Cheng Z et al. 2013. Influence of energy balance on the antimicrobial peptides S100A8 and S100A9 in the endometrium of the post-partum dairy cow. Reproduction 145:527–39
     [Google Scholar]
105. 105.  Ledgard AM, Smolenski GA, Henderson H, Lee RS 2015. Influence of pathogenic bacteria species present in the postpartum bovine uterus on proteome profiles. Reprod. Fertil. Dev. 27:395–406
     [Google Scholar]
106. 106.  Lemaitre B, Nicolas E, Michaut L, Reichhart JM, Hoffmann JA 1996. The dorsoventral regulatory gene cassette spätzle/Toll/cactus controls the potent antifungal response in Drosophila adults. Cell 86:973–83Discovery of a role for Toll in invertebrates, founding the field of innate immunity.
     [Google Scholar]
107. 107.  Poltorak A, He X, Smirnova I, Liu MY, Huffel CV et al. 1998. Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in Tlr4 gene. Science 282:2085–88Discovery of a role for Tlr4 in recognition of LPS in mice, founding the field of innate immunity in mammals.
     [Google Scholar]
108. 108.  Schroder K, Tschopp J 2010. The inflammasomes. Cell 140:821–32
     [Google Scholar]
109. 109.  Herath S, Fischer DP, Werling D, Williams EJ, Lilly ST et al. 2006. Expression and function of Toll-like receptor 4 in the endometrial cells of the uterus. Endocrinology 147:562–70First evidence for the role of innate immunity in bovine endometrial cells.
     [Google Scholar]
110. 110.  Cronin JG, Turner ML, Goetze L, Bryant CE, Sheldon IM 2012. Toll-Like receptor 4 and MyD88-dependent signaling 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
     [Google Scholar]
111. 111.  Turner ML, Cronin JC, Healey GD, Sheldon IM 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 155:1453–65
     [Google Scholar]
112. 112.  MacKintosh SB, Schuberth HJ, Healy LL, Sheldon IM 2013. Polarised bovine endometrial epithelial cells vectorially secrete prostaglandins and chemotactic factors under physiological and pathological conditions. Reproduction 145:57–72
     [Google Scholar]
113. 113.  Healy LL, Cronin JG, Sheldon IM 2015. Polarized epithelial cells secrete interleukin 6 apically in the bovine endometrium. Biol. Reprod. 92:151
     [Google Scholar]
114. 114.  Herath S, Lilly ST, Fischer DP, Williams EJ, Dobson H et al. 2009. Bacterial lipopolysaccharide induces an endocrine switch from prostaglandin F_2a to prostaglandin E₂ in bovine endometrium. Endocrinology 150:1912–20
     [Google Scholar]
115. 115.  Blander JM, Sander LE 2012. Beyond pattern recognition: five immune checkpoints for scaling the microbial threat. Nat. Rev. Immunol. 12:215–25
     [Google Scholar]
116. 116.  Cronin JG, Kanamarlapudi V, Thornton CA, Sheldon IM 2016. Signal transducer and activator of transcription-3 licenses Toll-like receptor 4-dependent interleukin (IL)-6 and IL-8 production via IL-6 receptor-positive feedback in endometrial cells. Mucosal Immunol 9:1125–36
     [Google Scholar]
117. 117.  Chen GY, Nuñez G 2010. Sterile inflammation: sensing and reacting to damage. Nat. Rev. Immunol. 10:826–37
     [Google Scholar]
118. 118.  Matzinger P 2002. The danger model: a renewed sense of self. Science 296:301–5
     [Google Scholar]
119. 119.  McNeela EA, Burke Á, Neill DR, Baxter C, Fernandes VE et al. 2010. Pneumolysin activates the NLRP3 inflammasome and promotes proinflammatory cytokines independently of TLR4. PLOS Pathog 6:e1001191
     [Google Scholar]
120. 120.  Gurcel L, Abrami L, Girardin S, Tschopp J, van der Goot FG 2006. Caspase-1 activation of lipid metabolic pathways in response to bacterial pore-forming toxins promotes cell survival. Cell 126:1135–45
     [Google Scholar]
121. 121.  Kvidera SK, Horst EA, Abuajamieh M, Mayorga EJ, Fernandez MV, Baumgard LH 2017. Glucose requirements of an activated immune system in lactating Holstein cows. J. Dairy Sci. 100:2360–74
     [Google Scholar]
122. 122.  Dhaliwal GS, Murray RD, Woldehiwet Z 2001. Some aspects of immunology of the bovine uterus related to treatments for endometritis. Anim. Reprod. Sci. 67:135–52
     [Google Scholar]
123. 123.  Machado VS, Bicalho MLS, Gilbert RO, Bicalho RC 2014. Short communication: relationship between natural antibodies and postpartum uterine health in dairy cows. J. Dairy Sci. 97:7674–78
     [Google Scholar]
124. 124.  Nolte O, Morscher J, Weiss HE, Sonntag H 2001. Autovaccination of dairy cows to treat post partum metritis caused by Actinomycespyogenes. . Vaccine 19:3146–53
     [Google Scholar]
125. 125.  Machado VS, Bicalho ML, Meira Junior EB, Rossi R, Ribeiro BL et al. 2014. Subcutaneous immunization with inactivated bacterial components and purified protein of Escherichia coli, Fusobacteriumnecrophorum and Trueperellapyogenes prevents puerperal metritis in Holstein dairy cows. PLOS ONE 9:e91734
     [Google Scholar]
126. 126.  Freick M, Kunze A, Passarge O, Weber J, Geidel S 2017. Metritis vaccination in Holstein dairy heifers using a herd-specific multivalent vaccine: effects on uterine health and fertility in first lactation. Anim. Reprod. Sci. 184:160–71
     [Google Scholar]
127. 127.  Kamimura S, Ohgi T, Takahashi M, Tsukamoto T 1993. Postpartum resumption of ovarian activity and uterine involution monitored by ultrasonography in Holstein cows. J. Vet. Med. Sci. 55:643–47
     [Google Scholar]
128. 128.  Sheldon IM, Dobson H 2000. Effect of administration of eCG to postpartum cows on folliculogenesis in the ovary ipsilateral to the previously gravid uterine horn and uterine involution. J. Reprod. Fertil. 119:157–63
     [Google Scholar]
129. 129.  Williams EJ, Fischer DP, Noakes DE, England GC, Rycroft A et al. 2007. The relationship between uterine pathogen growth density and ovarian function in the postpartum dairy cow. Theriogenology 68:549–59
     [Google Scholar]
130. 130.  Green MP, Ledgard AM, Beaumont SE, Berg MC, McNatty KP et al. 2011. Long-term alteration of follicular steroid concentrations in relation to subclinical endometritis in postpartum dairy cows. J. Anim. Sci. 89:3551–60
     [Google Scholar]
131. 131.  Hixon JE, Hansel W 1974. Evidence for preferential transfer of prostaglandin F2alpha to the ovarian artery following intrauterine administration in cattle. Biol. Reprod. 11:543–52
     [Google Scholar]
132. 132.  Herath S, Williams EJ, Lilly ST, Gilbert RO, Dobson H et al. 2007. Ovarian follicular cells have innate immune capabilities that modulate their endocrine function. Reproduction 134:683–93Finding of LPS in ovarian follicular fluid and recognition that bovine granulosa cells have roles in innate immunity.
     [Google Scholar]
133. 133.  Magata F, Horiuchi M, Echizenya R, Miura R, Chiba S et al. 2014. Lipopolysaccharide in ovarian follicular fluid influences the steroid production in large follicles of dairy cows. Anim. Reprod. Sci. 144:6–13
     [Google Scholar]
134. 134.  Cheong SH, Sa Filho OG, Absalon-Medina VA, Schneider A, Butler WR, Gilbert RO 2017. Uterine and systemic inflammation influences ovarian follicular function in postpartum dairy cows. PLOS ONE 12:e0177356
     [Google Scholar]
135. 135.  Bromfield JJ, Sheldon IM 2011. Lipopolysaccharide initiates inflammation in bovine granulosa cells via the TLR4 pathway and perturbs oocyte meiotic progression in vitro. . Endocrinology 152:5029–40
     [Google Scholar]
136. 136.  Price JC, Bromfield JJ, Sheldon IM 2013. Pathogen-associated molecular patterns initiate inflammation and perturb the endocrine function of bovine granulosa cells from ovarian dominant follicles via TLR2 and TLR4 pathways. Endocrinology 154:3377–86
     [Google Scholar]
137. 137.  Price JC, Sheldon IM 2013. Granulosa cells from emerged antral follicles of the bovine ovary initiate inflammation in response to bacterial pathogen-associated molecular patterns via Toll-like receptor pathways. Biol. Reprod. 89:119
     [Google Scholar]
138. 138.  Alpizar E, Spicer LJ 1994. Effects of interleukin-6 on proliferation and follicle-stimulating hormone-induced estradiol production by bovine granulosa cells in vitro: dependence on size of follicle. Biol. Reprod. 49:38–43
     [Google Scholar]
139. 139.  Spicer LJ 1998. Tumor necrosis factor-α (TNF-α) inhibits steroidogenesis of bovine ovarian granulosa and thecal cells in vitro. Involvement of TNF-α receptors. Endocrine 8:109–15
     [Google Scholar]
140. 140.  Shimizu T, Kaji A, Murayama C, Magata F, Shirasuna K et al. 2012. Effects of interleukin-8 on estradiol and progesterone production by bovine granulosa cells from large follicles and progesterone production by luteinizing granulosa cells in culture. Cytokine 57:175–81
     [Google Scholar]
141. 141.  Bromfield JJ, Sheldon IM 2013. Lipopolysaccharide reduces the primordial follicle pool in the bovine ovarian cortex ex vivo and in the murine ovary in vivo. Biol. Reprod. 88:98
     [Google Scholar]
142. 142.  Sheldon IM, Price JC, Turner ML, Bromfield JJ, Cronin GJ 2014. Uterine infection and immunity in cattle. Reproduction in Domestic Ruminants VIII JL Juengel, A Miyamoto, C Price, LP Reynolds, RF Smith, R Webb 415–30 Ashby-de-la-Zouch, UK: Context Prod
     [Google Scholar]
143. 143.  Britt JH 1992. Impacts of early postpartum metabolism on follicular development and fertility. Bov. Pract. 24:39–43
     [Google Scholar]
144. 144.  Karsch FJ, Battaglia DF, Breen KM, Debus N, Harris TG 2002. Mechanisms for ovarian cycle disruption by immune/inflammatory stress. Stress 5:101–12
     [Google Scholar]
145. 145.  Suzuki C, Yoshioka K, Iwamura S, Hirose H 2001. Endotoxin induces delayed ovulation following endocrine aberration during the proestrous phase in Holstein heifers. Domest. Anim. Endocrinol. 20:267–78
     [Google Scholar]
146. 146.  Lavon Y, Leitner G, Goshen T, Braw-Tal R, Jacoby S, Wolfenson D 2008. Exposure to endotoxin during estrus alters the timing of ovulation and hormonal concentrations in cows. Theriogenology 70:956–67
     [Google Scholar]
147. 147.  Lewis GS 2003. Steroidal regulation of uterine resistance to bacterial infection in livestock. Reprod. Biol. Endocrinol. 1:117
     [Google Scholar]
148. 148.  Sheldon IM, Noakes DE, Rycroft AN, Dobson H 2004. Effect of intrauterine administration of oestradiol on postpartum uterine bacterial infection in cattle. Anim. Reprod. Sci. 81:13–23
     [Google Scholar]
149. 149.  Saut JP, Healey GD, Borges AM, Sheldon IM 2014. Ovarian steroids do not impact bovine endometrial cytokine/chemokine responses to E. coli or LPS in vitro. . Reproduction 148:593–606
     [Google Scholar]