Martin Sheldon FRCVS
Professor Emeritus
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Biography
Biography
Martin Sheldon qualified as a veterinary surgeon in 1984 (BVSc, MRCVS), and was awarded two Diplomas (DBR, DCHP) whilst working in clinical practice in Wales. He moved to the Royal Veterinary College, London in 1998, becoming Professor of Veterinary Reproduction. He also completed a PhD thesis on postpartum uterine disease in 2002, supervised by Prof Hilary Dobson at the University of Liverpool. Prof Sheldon was awarded a BBSRC Research Development Fellowship in 2005, FRCVS for meritorious contributions to research in 2013, and the Schofield Prize in 2015. He was Professor of Reproductive Immunobiology at Swansea University Medical School between 2008 and 2024.
Research Interests
Research Interests
Resilience - Immunology - Infection - Reproduction
Resilience - Immunology - Infection - Reproduction
Prof Sheldon discovered that ovarian function is perturbed in animals with uterine bacterial co-infections. He initially worked out how the main pathogenic bacteria cause co-infections that lead to inflammation and tissue damage in the endometrium, and how this infection and inflammation affects the ovary. Key discoveries were that the epithelial and stromal cells of the endometrium, and the granulosa cells of the ovary have roles in innate immunity. These cells express receptors, such as Toll-like Receptors (TLRs), which detect pathogen-associated molecular patterns to induce inflammatory responses, including the production of cytokines, chemokines and prostaglandins. Furthermore, pathogen-associated molecules impair oocyte health and perturb embryo development. These findings link bacterial infections to long-term impacts on fertility.
Prof Sheldon also explored the impact on tissues of pore-forming toxins, which are the most common virulence factor used by bacteria to damage host cells. He found that cells can be protected against pore-forming toxins by manipulating the cholesterol biosynthesis and homeostasis pathways, using statins, LXR agonists, or oxysterols. Finding ways to protect cells against bacterial virulence factors is an alternative to using antimicrobials to kill bacteria, which helps in the fight against antimicrobial resistance.
Finally, Prof Sheldon worked on how the endocrine system and hormones affect host resilience. It is well-established that the female sex hormones and corticosteroids affect immunity, but the mechanisms are not clear. Progesterone helps establish infections in the uterus, but endometrial cell immune responses were not affected by the female sex hormones. However, corticosteroids and oxysterols stimulate the intrinsic protection of tissue cells against pathogens to improve host resilience. Oxysterols likely act as signaling molecules so that cells exposed to pathogens secrete oxysterols to enhance the resilience of nearby cells.
Selected publications
Selected publications
Ormsby TJR, Owens SE, Horlock AD, Davies D, Griffiths WJ, Wang Y, Cronin JG, Bromfield JJ, Sheldon IM. 2021 Oxysterols protect bovine endometrial cells against pore-forming toxins from pathogenic bacteria. The FASEB Journal 35:e21889.
Horlock AD, Piersanti RL, Ramirez-Hernandez R, Yu F, Ma Z, Jeong KC, Clift MJD, Block J, Santos JEP, Bromfield JJ, Sheldon IM. 2020 Uterine infection alters the transcriptome of the bovine reproductive tract three months later. Reproduction 160(1):93-107
Pospiech M, Owens SE, Miller DJ, Austin-Muttitt K, Mullins JGL, Cronin JG, Allemann RK, Sheldon IM. 2021. Bisphosphonate inhibitors of squalene synthase protect cells against cholesterol-dependent cytolysins. The FASEB Journal 35(6), e21640.
Sheldon IM, Cronin JG, Bromfield JJ. 2019 Tolerance and Innate Immunity Shape the Development of Postpartum Uterine Disease and the Impact of Endometritis in Dairy Cattle. Annual Review of Animal Biosciences, 7, 361-384
Amos MR, Healey GD, Goldstone RJ, Mahan SM, Düvel A, Schuberth HJ, Sandra O, Zieger P, Dieuzy-Labaye I, Smith DGE, Sheldon IM 2014 Differential Endometrial Cell Sensitivity to a Cholesterol-Dependent Cytolysin Links Trueperella pyogenes to Uterine Disease in Cattle. Biology of Reproduction 90, 54, 1-13
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. Biology of Reproduction 86: 51
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: 5029-5040
Herath S, Williams EJ, Lilly ST, Gilbert RO, Dobson H, Bryant CE, Sheldon IM, 2007 Ovarian follicular cells have innate immune capabilities that modulate their endocrine function. Reproduction 134: 683-693
Herath S, Fischer DP, Werling D, Williams EJ, Lilly ST, Dobson H, Bryant CE, Sheldon IM, 2006 Expression and function of Toll-like receptor 4 in the endometrial cells of the uterus. Endocrinology 147:562-570
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 123:837-845
See below for full list of publications
Funding
Funding
BBSRC, NIH (USA), NRN (Wales), the Royal Society, Wellcome Trust, OECD, industry, and the RCVS.
Science
Science
Uterine disease impairs ovarian function and ooctye health
Uterine disease impairs ovarian function and ooctye health
Uterine disease reduces ovarian follicle growth rates, the likelihood of ovulation, damages oocytes, and the proportion of oocytes that developed to morulae following in vitro fertilization.
For more details see: 10.1093/biolre/ioaa069 10.1210/en.2011-1124 and 10.1530/rep.0.1230837
Improving resilience against pathogenic bacteria
Improving resilience against pathogenic bacteria
Resilient animals prevent the development of disease by avoiding, tolerating and resisting infection.
For more details see: 10.1016/j.theriogenology.2020.01.017 ).
Avoiding, tolerating and resisting pathogenic bacteria
Avoiding, tolerating and resisting pathogenic bacteria
Preventing postpartum uterine disease
Preventing postpartum uterine disease
For more details see:
Impact
Impact
Protecting tissues against damage caused by bacteria
Tissue damage is a common feature of bacterial diseases. Many species of pathogenic bacteria produce toxins that form holes in cell membranes, which can cause cell death. However, tissue cells vary in their ability to protect themselves against these toxins. Furthermore, hormones and drugs can increase the resilience of cell membranes to pore-forming toxins.
Uterine infection and infertility in dairy cows
Bacterial infections of the uterus are a worldwide problem for dairy cows because they cause disease and infertility in more than 40% of animals. Infections disrupt the function of the uterus and impair the health of eggs in the ovary. Improving animal welfare depends on increasing the resilience of cows to infections, and by developing novel approaches for the treatment and prevention of disease.
Seekford ZK, Tariq A, Macay GA, Jenkins KM, Dickson MJ, Melo GD, Pohler KG, Sheldon IM, Bromfield JJ. Uterine disease in dairy cows is associated with contemporaneous perturbations to ovarian function. Theriogenology 2024. doi: 10.1016/j.theriogenology.2024.10.028
Farook MR, Croxford Z, Morgan S, Horlock AD, Holt A, Rees A, Jenkins BJ, Tse C, Stanton E, Davies DM, Thornton CA, Jones N, Sheldon IM, Vincent EE, Cronin JG. Loss of mitochondrial pyruvate carrier 1 supports proline-dependent proliferation and collagen biosynthesis in ovarian cancer. Mol Metab. 2024 Feb 13:101900. doi: 10.1016/j.molmet.2024.101900.
Ormsby TJR, Owens SE, Turner ML, Cronin JG, Bromfield JJ, Sheldon IM. 2023 Glucocorticoids increase tissue cell protection against pore-forming toxins from pathogenic bacteria. Nature Communications Biology 6, 186 Open Access
Husnain A, Arshad U, Zimpel R, Schmitt E, Dickson MJ, Perdomo MC, Marinho MN, Ashrafi N, Graham SF, Bishop JV, Hansen TR, Jeong KC, Gonella-Diaza AM, Chebel RC, Sheldon IM, Bromfield JJ, Santos JEP. Induced endometrial inflammation compromises conceptus development in dairy cattle†. Biol Reprod. 2023 Oct 13;109(4):415-431.
Husnain A, Arshad U, Poindexter MB, Zimpel R, Marinho MN, Perdomo MC, Fan P, Jeong KC, Nelson CD, Sheldon IM, Bromfield JJ, Santos JEP. Induced endometritis in early lactation compromises production and reproduction in dairy cows. J Dairy Sci. 2023 Apr 18:S0022-0302(23)00183-2. doi: 10.3168/jds.2022-2284
Horlock AD, Ormsby TJR, Clift MJD, Santos JEP, Bromfield JJ, Sheldon IM. 2022 Cholesterol supports bovine granulosa cell inflammatory responses to lipopolysaccharide. Reproduction. 2022 Aug 5;164(3):109-123.
Ormsby TJR, Owens SE, Clement L, Mills TJ, Cronin JG, Bromfield JJ & Sheldon IM 2022 Oxysterols Protect Epithelial Cells Against Pore-Forming Toxins. Frontiers in Immunology 13 815775 Open Access
Molinari PCC, Davidson BD, Laporta J, Dahl GE, Sheldon IM, Bromfield JJ. 2022 Prepartum heat stress in dairy cows increases postpartum inflammatory responses in blood of lactating dairy cows. J Dairy Sci. 2022 Nov 29:S0022-0302(22)00701-9. doi: 10.3168/jds.2022-22405.
Dickson MJ, Sheldon IM, Bromfield JJ 2022 Lipopolysaccharide alters CEBPβ signaling and reduces estradiol production in bovine granulosa cells. CABI Agriculture and Bioscience 3, 66
Molinari PCC, Dahl GE, Sheldon IM, Bromfield JJ. 2022 Effect of calving season on metritis incidence and bacterial content of the vagina in dairy cows. Theriogenology, 191:67-76.
Dickson MJ, Bishop JV, Hansen TR, Sheldon IM, Bromfield JJ. The endometrial transcriptomic response to pregnancy is altered in cows after uterine infection. PLoS One. 2022 Mar 31;17(3):e0265062
Abdullaeva M, Bromfield JJ, Sheldon IM 2022 Expansion of information in scientific research papers. bioRxiv 2022.05.06.490896. Open Access
Ormsby TJR, Owens SE, Horlock AD, Davies D, Griffiths WJ, Wang Y, Cronin JG, Bromfield JJ, Sheldon IM. 2021 Oxysterols protect bovine endometrial cells against pore-forming toxins from pathogenic bacteria. The FASEB Journal. 35:e21889. Open Access
Pospiech, M., Owens, S. E., Miller, D. J., Austin-Muttitt, K., Mullins, J.G.L., Cronin, J. G., Allemann, R. K., & Sheldon, I. M. (2021). Bisphosphonate inhibitors of squalene synthase protect cells against cholesterol-dependent cytolysins. FASEB Journal 35(6), e21640. Open Access
Horlock AD, Ormsby TJR, Clift MJD, Santos JEP, Bromfield JJ, Sheldon IM. 2021 Manipulating bovine granulosa cell energy metabolism limits inflammation. Reproduction 161(5):499-512
Chaney HL, Grose LF, Charpigny G, Behura SK, Sheldon IM, Cronin JG, Lonergan P, Spencer TE, Mathew DJ. 2021 Conceptus-induced, interferon tau dependent gene expression in bovine endometrial epithelial and stromal cells. Biology of Reproduction 104(3):669-683
Britt, J. H., Cushman, R. A., Dechow, C. D., Dobson, H., Humblot, P., Hutjens, M. F., Jones, G. A., Mitloehner, F. M., Ruegg, P. L., Sheldon, I. M., and Stevenson, J. S. (2021) Review: Perspective on high-performing dairy cows and herds. Animal, 100298 Open Access
Sheldon IM, Molinari PCC, Ormsby TJR, Bromfield JJ. 2020 Preventing postpartum uterine disease in dairy cattle depends on avoiding, tolerating and resisting pathogenic bacteria. Theriogenology 150, 158-165 PDF
Piersanti RL, Block J, Ma Z, Jeong KC, Santos JEP, Yu F, Sheldon IM, Bromfield JJ. Uterine infusion of bacteria alters the transcriptome of bovine oocytes. FASEB BioAdvances 2(8), 506-520 Open Access
Horlock AD, Piersanti RL, Ramirez-Hernandez R, Yu F, Ma Z, Jeong KC, Clift MJD, Block J, Santos JEP, Bromfield JJ, Sheldon IM. 2020 Uterine infection alters the transcriptome of the bovine reproductive tract three months later. Reproduction 160(1):93-107 PDF
Dickson MJ, Piersanti RL, Ramirez-Hernandez R, de Oliveira EB, Bishop JV, Hansen TR, Ma Z, Jeong KC, Santos JEP, Sheldon IM, Block J, Bromfield JJ. 2020 Experimentally induced endometritis impairs the developmental capacity of bovine oocytes. Biology of Reproduction 2020 Volume 103, Issue 3, September 2020, Pages 508–520, PDF
Turner ML, Owens SE, Sheldon IM. 2020 Glutamine supports the protection of tissue cells against the damage caused by cholesterol-dependent cytolysins from pathogenic bacteria. PLoS ONE 15(3): e0219275. Open Access
Eozenou C, Lesage-Padilla A, Mauffré V, Healey GD, Camous S, Bolifraud P, Giraud-Delville C, Vaiman D, Shimizu T, Miyamoto A, Sheldon IM, Constant F, Pannetier M, Sandra O. 2020 FOXL2 is a Progesterone Target Gene in the Endometrium of Ruminants. Int J Mol Sci. 2020 Feb 21;21(4). pii: E1478. Open Access
Sheldon, IM. 2020 Diagnosing postpartum endometritis in dairy cattle Veterinary Record 186, 88-90.
Piersanti RL Santos JE.P, Sheldon IM, Bromfield JJ. 2019 Lipopolysaccharide and tumor necrosis factor-alpha alter gene expression of oocytes and cumulus cells during bovine in vitro maturation. Molecular Reproduction and Development 86(12) 1909-1920 PDF
Sheldon IM, Molinari PCC, Ormsby TJR, Bromfield JJ. 2019 Preventing Postpartum Uterine Disease in Dairy Cattle Depends on Avoiding, Tolerating and Resisting Pathogenic Bacteria. Preprints, 2019080140 (doi: 10.20944/preprints201908.0140.v1). Open Access PREPRINT (not peer reviewed)
Raliou M, Dembélé D, Düvel A, Bolifraud P, Aubert J, Mary-Huard T, Rocha D, Piumi F, Mockly S, Heppelmann M, Dieuzy-Labaye I, Zieger P, G E Smith D, Schuberth HJ, Sheldon IM, Sandra O. 2019 Subclinical endometritis in dairy cattle is associated with distinct mRNA expression patterns in blood and endometrium. PLoS One. 14(8):e0220244. doi: 10.1371/journal.pone.0220244. Open Access PDF
Turner ML, Owens SE, Sheldon IM. 2019 Glutamine supports the protection of tissue cells against the damage caused by cholesterol-dependent cytolysins from pathogenic bacteria. bioRxiv 10.1101/679068 Open Access PREPRINT (not peer reviewed)
Piersanti RL, Horlock AD, Block J, Santos JEP, Sheldon IM, Bromfield JJ. 2019 Persistent effects on bovine granulosa cell transcriptome after resolution of uterine disease. Reproduction, 158, 35-46 PDF available
Carvalho AV, Eozenou C, Richard C, Forde N, Healey GD, Giraud-Delville C, Mansouri-Attia N, Lonergan P, Sheldon IM, Sandra O. 2019 Bovine scavenger receptor class A (SR-A) exhibit specific patterns of regulation in the endometrium during the oestrous cycle and early pregnancy. Reproduction, Fertility and Development 31(6) 1078-1090
Pisano S, Giustiniani M, Francis L, Gonzalez D, Margarit L, Sheldon IM, Paolino D, Fresta M, Conlan RS, Healey GD. 2019 Liquid crystal delivery of ciprofloxacin to treat infections of the female reproductive tract. Biomed Microdevices. Mar 29;21(2):36. doi: 10.1007/s10544-019-0385-x. Open Access
Sheldon IM, Cronin JG, Bromfield JJ (2019) Tolerance and Innate Immunity Shape the Development of Postpartum Uterine Disease and the Impact of Endometritis in Dairy Cattle. Annual Review of Animal Biosciences, 7, 361-384. 10.1146/annurev-animal-020518-115227 Request a copy
Sheldon IM (2018) Chapter 23: The Metritis Complex in Cattle. Veterinary Reproduction & Obstetrics 10th Edition, WB Saunders. 408-433 Request copy
Piersanti RL, Zimpel R, Molinari PCC, Dickson MJ, Ma Z, Jeong KCC, Santos JEP, Sheldon IM, Bromfield JJ 2019 A model of clinical endometritis in Holstein heifers using pathogenic Escherichia coli and Trueperella pyogenes. Journal of Dairy Science, 102(3), 2686-2697 Request a copy
Griffin S, Healey GD, Sheldon IM. 2018 Isoprenoids increase bovine endometrial stromal cell tolerance to the cholesterol-dependent cytolysin from Trueperella pyogenes. Biology of Reproduction, 2018, 99(4), 749–760 Open Access PDF
Sheldon, IM.(2018) Metabolic stress and endometritis in dairy cattle. Veterinary Record, 183, 124-125. PDF
Britt JH, Cushman RA, Dechow CD, Dobson H, Humblot P, Hutjens MF, Jones GA, Ruegg PS, Sheldon IM, Stevenson JS. 2018 Invited review: Learning from the future-A vision for dairy farms and cows in 2067. Journal of Dairy Science, 101:3722-3741. Open Access PDF
Sheldon IM, Cronin JG, Pospiech M, Turner ML. 2018 Symposium review: Mechanisms linking metabolic stress with innate immunity in the endometrium. Journal of Dairy Science,101: 3655-3664 Open access PDF
Griffin S, Preta G, Sheldon, IM 2017 Inhibiting mevalonate pathway enzymes increases stromal cell resilience to a cholesterol-dependent cytolysin. Scientific Reports 7, 17050, p 1-13 Open Access PDF
Lesage-Padilla A, Forde N, Poirée M, Healey GD, Giraud-Delville C, Reinaud P, Eozenou C, Vitorino Carvalho A, Galio L, Raliou M, Oudin J-F, Richard C, Sheldon IM, Charpigny G, Lonergan P, Sandra O. (2017). Maternal metabolism affects endometrial expression of oxidative stress and FOXL2 genes in cattle. PLOS ONE 12(12), e0189942 Open Access PDF
Sheldon, I. & Owens, S 2017 Postpartum uterine infection and endometritis in dairy cattle. Animal Reproduction vol. 14 no. 3 pp. 622 - 629 Open Access PDF
Carneiro L, Bedford C, Jacca S, Rosamilia A, Lima V, Donofrio G, Sheldon IM, Cronin J. 2017 Coordinated Role of Toll-Like Receptor-3 and Retinoic Acid-Inducible Gene-I in the Innate Response of Bovine Endometrial Cells to Virus. Frontiers in Immunology 8: 996, 1-11. Open Access
Noleto PG, Saut JPE, Sheldon IM 2017 Short communication: Glutamine modulates inflammatory responses to lipopolysaccharide in ex vivo bovine endometrium. Journal of Dairy Science 100: 2207-2212. Open Access PDF
Sheldon, IM, Owens, SE, Turner, ML 2017 Innate immunity and the sensing of infection, damage and danger in the female genital tract. Journal of Reproductive Immunology 119: 67–73 PDF
Gadsby JE, Tyson Nipper AM, Faircloth HA, D'Annibale-Tolhurst M, Chang J, Farin PW, Sheldon IM, Poole DH. 2017 Toll-like receptor and related cytokine mRNA expression in bovine corpora lutea during the oestrous cycle and pregnancy. Reprod Domest Anim. 52:495-504.
Cronin JG, Kanamarlapudi V, Thornton CA, Sheldon IM. 2016 Signal transducer and activator of transcription-3 (STAT3) licenses Toll-like receptor 4-dependent Interleukin (IL)-6 and IL-8 production via IL-6 receptor positive feedback in endometrial cells. Mucosal Immunology, 9, 1125-1136 Open Access PDF
Sheldon, IM (2016) Detection of Pathogens in Blood for Diagnosis of Sepsis and Beyond EBioMedicine, 9, 13-14
Healey GD, Collier C, Griffin S, Schuberth HJ,Sandra O, Smith DG, Mahan s, Dieuzy-Labaye I Sheldon IM 2016 Mevalonate biosynthesis intermediates are key regulators of innate immunity in bovine endometritis Journal of Immunology 196:823-831 Open Access PDF Supplemental Information PMC version of Open Access paper
Turner ML, Cronin J.G, 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(3): e0151416. doi:10.1371/journal.pone.0151416 Open access PDF
Carneiro LC, Cronin JG, Sheldon IM 2016 Mechanisms linking bacterial infections of the bovine endometrium to disease and infertility. Reproductive Biology 16:1-7 PDF
Preta G, Jankuneca M, Heinrich F, Griffin S, Sheldon IM, Valinciusa B 2016 Tethered bilayer membranes as a complementary tool for functional and structural studies: The pyolysin case. Biochimica et Biophysica Acta Biomembranes 1858: 2070–2080 PDF
Preta G, Lotti V, Cronin JG, Sheldon IM 2015 Protective role of the dynamin inhibitor Dynasore against the cholesterol-dependent cytolysin ofTrueperella pyogenes FASEB Journal 29(4), 1516-1528 Open Access PDF
Healy LL, Cronin JG, Sheldon IM. 2015 Polarized Epithelial Cells Secrete Interleukin 6 Apically in the Bovine Endometrium. Biology of Reproduction 92:151, 1–12 Open Access PDF
MacKintosh SB, Serino LP, Iddon PD, Brown R, Conlan RS, Wright CJ, Maffeis TG, Raxworthy MJ, Sheldon IM. 2015 A three-dimensional model of primary bovine endometrium using an electrospun scaffold. Biofabrication, 7:025010 PDF Open Access Preprint
Bromfield, JJ, Santos, J., Block, J., Williams, R. & Sheldon, IM 2015 PHYSIOLOGY AND ENDOCRINOLOGY SYMPOSIUM: Uterine infection: Linking infection and innate immunity with infertility in the high-producing dairy cow Journal of Animal Science, 93:2021-2033 PDF
Preta G, Cronin JG, Sheldon IM 2015 Dynasore - not just a dynamic inhibitor Cell Communication and Signaling 2015, 13:24 Open Access PDF
Sheldon IM 2015 Milk somatic cell counts and pregnancy rates in dairy cattle Veterinary Record 176: 409-410
Cronin JG, Hodges R, Pedersen S, Sheldon IM 2015 Enzyme Linked Immunosorbent Assay for Quantification of Bovine Interleukin-8 to Study Infection and Immunity in the Female Genital Tract American Journal of Reproductive Immunology 73, 372-382
Sheldon IM 2015 Genes and environmental factors that influence disease resistance to microbes in the female reproductive tract of dairy cattle. Reproduction, Fertility and Development 27 (1), 72-81 Open Access Preprint
Amos MR, Healey GD, Goldstone RJ, Mahan SM, Düvel A, Schuberth HJ, Sandra O, Zieger P, Dieuzy-Labaye I, Smith DGE, Sheldon IM 2014 Differential Endometrial Cell Sensitivity to a Cholesterol-Dependent Cytolysin Links Trueperella pyogenes to Uterine Disease in Cattle. Biology of Reproduction 90, 54, 1-13 Open Access PDF
Turner ML, Cronin J.G, 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, 155:1453-1465 Open Access PDF
Turner ML, Cronin J.G, 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, 155:1453-1465 Open Access PDF
Healy LL, Cronin JG, Sheldon IM 2014 Endometrial cells sense and react to tissue damage during infection of the bovine endometrium via interleukin 1. Scientific Reports, 4: 7060, 1-9 Open Access PDF
Cronin J.G, Healey GD, MacKintosh SBP, Turner ML, Healy LL, Sheldon IM, 2014 Bovine Endometrial Epithelial and Stromal Cells -Standard Operating Procedures for Isolation and Culture of Primary Bovine Endometrial Epithelial and Stromal Cells DOI: 10.13140/RG.2.2.29160.11529 Available Here
Goldstone RJ, Popat R, Schuberth HJ, Sandra O, Sheldon IM, Smith DG. 2014 Genomic characterisation of an endometrial pathogenic Escherichia coli strain reveals the acquisition of genetic elements associated with extra-intestinal pathogenicity. BMC Genomics, 15:1075 Open Access PDF
Sheldon IM, Cronin JG, Healey GD, Gabler C, Heuwieser W, Streyl D, Bromfield J, Miyamoto A, Fergani C, Dobson H 2014 Innate immunity and inflammation of the bovine female reproductive tract in health and disease Reproduction 148, R41-R51 Open Access PDF
Goldstone RJ, Talbot R, Schuberth HJ, Sandra O, Sheldon IM, Smith DG. 2014 Draft Genome Sequence of Escherichia coli MS499, Isolated from theInfected Uterus of a Postpartum Cow with Metritis. Genome Announcements 2014 Jul 3;2, e00217-14 Open Access PDF
Goldstone RJ, Amos M, Talbot R, Schuberth HJ, Sandra O, Sheldon IM, Smith DG. 2014 Draft genome sequence of Trueperella pyogenes, isolated from the infected uterus of a postpartum cow with metritis Genome Announcements 2 (2), e00194-14 Open Access PDF
Saut JPE, 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
Sheldon IM, Price JC, Turner ML, Bromfield JJ, Cronin JJ 2014 Uterine infection and immunity in cattle. In “Reproduction in DomesticRuminants VIII”, pp 415-430. Editors: Juengel JJ, Miyamoto A, Price C, Reynolds LP, Smith MF, Webb R. Published by Context Products Ltd, Ashby de la Zouch, UK. Open Access PDF
Carvalho AV, Reinaud P, Forde N, Healey GD, Eozenou C, Giraud-Delville C, Mansouri-Attia N, Gall L, Richard C, Lonergan P, Sheldon IM, Lea RG, Sandra O. 2014 SOCS genes expression during physiological and perturbed implantation in bovine endometrium. Reproduction. 148: 545-557
Carvalho AV, Eozenou C, Healey GD, Forde N, Reinaud P, Chebrout M, Gall L, Rodde N, Padilla AL, Delville CG, Leveugle M, Richard C, Sheldon IM, Lonergan P, Jolivet G, Sandra O 2014 Analysis of STAT1 expression and biological activity reveals interferon-tau-dependent STAT1-regulated SOCS genes in the bovine endometrium Reproduction, Fertility and Development 28(4) 459-474 http://dx.doi.org/10.1071/RD14034
Düvel A, Maaß J, Heppelmann M, Hussen J, Koy M, Piechotta M, Sandra O, Smith DGE, Sheldon IM, Dieuzy-Labaye I, Zieger P, Schuberth HJ 2014 Peripheral blood leukocytes of cows with subclinical endometritis show an altered cellular composition and gene expression. Theriogenology 81, 906-911
Price JC and 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. Biology of Reproduction, 89:119, 1–12 Open PDF
Price JC, Bromfield JJ and 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: 3377-3386 Open PDF F1000 recommendation
Bromfield JJ and Sheldon IM 2013 Lipopolysaccharide Reduces the Primordial Follicle Pool in the Bovine Ovarian Cortex Ex Vivo and in the Murine Ovary In Vivo Biology of Reproduction 88: 98
Jacca S, Franceschi V, Colagiorgi A, Sheldon M, and Donofrio G 2013 Bovine Endometrial Stromal Cells Support Tumor Necrosis Factor Alpha-Induced Bovine Herpesvirus Type 4 Enhanced Replication Biology of Reproduction 88:135.
Hussen J, Düvel A, Sandra O, Smith D, Sheldon IM, Zieger P, Schuberth HJ. 2013 Phenotypic and functional heterogeneity of bovine blood monocytes. PLoS One 8(8):e71502.
Beynon AL, Brown MR, Wright R, Rees MI, Sheldon IM, Davies JS. 2013 Ghrelin inhibits LPS-induced release of IL-6 from mouse dopaminergic neurones. J Neuroinflammation 10(1): 40
MacKintosh SBP, 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.
Turner ML, Healey GD, Sheldon IM, 2012 Immunity and Inflammation in the Uterus Reprod Dom Anim 47 (Suppl. 4), 402–409
Borges AM, Healey GD, Sheldon IM, 2012 Explants of Intact Endometrium to Model Bovine Innate Immunity and Inflammation Ex Vivo. American Journal of Reproductive Immunology 67: 526–539
Price JC, Cronin J, Sheldon IM, 2012 Toll-Like Receptor Expression and Function in the COV434 Granulosa Cell Line. American Journal of Reproductive Immunology 68: 205-217
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. Biology of Reproduction 86: 51
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: 5029-5040 Open Access PDF
Sheldon IM, Bromfield JJ. 2011 Innate immunity in the human endometrium and ovary. Am J Reprod Immunol. 66 Suppl 1: 63-71
Sheldon IM, Roberts MH, 2010 Toll-Like Receptor 4 Mediates the Response of Epithelial and Stromal Cells to Lipopolysaccharide in the Endometrium. PLoS ONE 5(9): e12906
Donofrio G, Capocefalo A, Franceschi V, Price S, Cavirani S, Sheldon IM, 2010 The Chemokine IL8 Is Up-Regulated in Bovine Endometrial Stromal Cells by the BoHV-4 IE2 Gene Product, ORF50/Rta: A Step Ahead Toward a Mechanism for BoHV-4 Induced Endometritis. Biology of Reproduction 83: 919-928
Sheldon IM, Rycroft AN, Dogan B, Craven M, Bromfield JJ, Chandler A, Roberts MH, Price SB, Gilbert RO, Simpson KW, 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(2): e9192
Potter TJ, Guitian J, Fishwick J, Gordon PJ, Sheldon IM. 2010 Risk factors for clinical endometritis in postpartum dairy cattle. Theriogenology.74:127-34.
Nash DM, Sheldon IM, Herath S, Lane EA. 2010 Markers of the uterine innate immune response of the mare. Animal Reproduction Science 119: 31-39
Herath S, Lilly ST, Fischer DP, Williams EJ, Dobson H, Bryant CE, Sheldon IM, 2009 Bacterial lipopolysaccharide induces an endocrine switch from prostaglandin F2a to prostaglandin E2 in bovine endometrium. Endocrinology 150:1912-1920
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. Biology of Reproduction 81:1025-1032
Herath S, Lilly ST, Santos NR, Gilbert RO, Goetze L, Bryant CE, White JO, Cronin J, Sheldon IM, 2009 Expression of genes associated with immunity in the endometrium of cattle with disparate postpartum uterine disease and fertility. Reproductive Biology and Endocrinology 7: 55
Donofrio G, Franceschi V, Capocefalo A, Cavirani S, Sheldon IM, 2009 Isolation and characterization of bovine herpesvirus 4 (BoHV-4) from a cow affected by post partum metritis and cloning of the genome as a bacterial artificial chromosome. Reproductive Biology and Endocrinology 7: 83
Sheldon IM, Price SB, Cronin J, Gilbert RO, Gadsby JE, 2009 Mechanisms of infertility associated with clinical and subclinical endometritis in high producing dairy cattle. Reproduction in Domestic Animals 44 Suppl 3:1-9
Nash D, Sheldon I, Herath S, Lane E, 2009 Endometrial Explant Culture to Study the Response of Equine Endometrium to Insemination. Reproduction in Domestic Animals 45: 670–676
Channon AJ, Walker AM, Pfau T, Sheldon IM, Wilson AM, 2009 Variability of Manson and Leaver locomotion scores assigned to dairy cows by different observers. Veterinary Record 164: 388-392
Donofrio G, Ravaneti L, Cavirani S, Herath S, Capocefalo A, Sheldon IM, 2008 Bacterial infection of endometrial stromal cells influences bovine herpesvirus 4 immediate early gene activation: a new insight into bacterial and viral interaction for uterine disease. Reproduction 136: 361-366
Williams EJ, Herath S, England GC, Dobson H, Bryant CE, Sheldon IM, 2008 Effect of Escherichia coli infection of the bovine uterus from the whole animal to the cell. Animal 2:1153-1157
Williams EJ, Sibley K, Miller ANA, Lane EA, Fishwick J, Nash DL, Herath S, England GC, Dobson H, Sheldon IM, 2008 The effect of Escherichia coli lipopolysaccharide and tumour necrosis factor alpha on ovarian function. American Journal of Reproductive Immunology 60: 462-473
Davies D, Meade KG, Herath S, Eckersall PD, Gonzalez D, White JO, Conlan RS, O'Farrelly C, Sheldon IM, 2008 Toll-like receptor and antimicrobial peptide expression in the bovine endometrium. Reproductive Biology and Endocrinology 6: 53
Sheldon IM, Williams EJ, Miller ANA, Nash DM, Herath S, 2008 Uterine diseases in cattle after parturition. Veterinary Journal 176:115-121
Nash DM, Lane EA, Herath S, Sheldon IM, 2008 Endometrial Explant Culture for Characterizing Equine Endometritis. American Journal of Reproductive Immunology 59:105-117
Cripps RL, Green LR, Thompson J, Martin-Gronert MS, Monk M, Sheldon I, Hanson MA, Hales, Ozanne SE, 2008 The Effect of Maternal Body Condition Score Before and During Pregnancy on the Glucose Tolerance of Adult Sheep Offspring. Reproductive Sciences 15: 448-456
Donofrio G, Franceschi V, Capocefalo A, Cavirani S, Sheldon IM, 2008 Bovine endometrial stromal cells display osteogenic properties. Reproductive Biology and Endocrinology 6: 65
Donofrio G, Herath S, Sartori C, Cavirani S, Flammini CF, Sheldon IM, 2007 Bovine herpesvirus 4 (BoHV-4) is tropic for bovine endometrial cells and modulates endocrine function. Reproduction 134:183-197
Herath S, Williams EJ, Lilly ST, Gilbert RO, Dobson H, Bryant CE, Sheldon IM, 2007 Ovarian follicular cells have innate immune capabilities that modulate their endocrine function. Reproduction 134: 683-693
Grant EJ, Lilly ST, Herath S, Sheldon IM, 2007 Escherichia coli lipopolysaccharide modulates bovine luteal cell function. Veterinary Record 161:695-696
Williams EJ, Fischer DP, Noakes DE, England GC, Rycroft A, Dobson H, Sheldon IM, 2007 The relationship between uterine pathogen growth density and ovarian function in the postpartum dairy cow. Theriogenology 68: 549-559
Perrin L, Bostelmann RW, Sheldon IM, 2007 Reduced conception rates associated with bovine mastitis during a 'window of opportunity'. Veterinary Record 161:61-62
Dobson H, Smith RF, Royal MD, Knight CH, Sheldon IM, 2007 The high producing dairy cow and its reproductive performance. Reproduction in Domestic Animals 42:17-23
Miller AN, Williams EJ, Sibley K, Herath S, Lane EA, Fishwick J, Nash DM, Rycroft AN, Dobson H, Bryant CE, Sheldon IM, 2007 The effects of Arcanobacterium pyogenes on endometrial function in vitro, and on uterine and ovarian function in vivo. Theriogenology 68:972-980
Herath S, Fischer DP, Werling D, Williams EJ, Lilly ST, Dobson H, Bryant CE, Sheldon IM, 2006 Expression and function of Toll-like receptor 4 in the endometrial cells of the uterus. Endocrinology 147:562-570
Herath S, Dobson H, Bryant CE, Sheldon IM, 2006 Use of the cow as a large animal model of uterine infection and immunity. Journal of Reproductive Immunology 69:13-22
Sheldon IM, Wathes DC, Dobson H, 2006 The management of bovine reproduction in elite herds. Veterinary Journal 171:70-78
Sheldon IM, Lewis GS, LeBlanc S, Gilbert RO, 2006 Defining postpartum uterine disease in cattle. Theriogenology 65:1516-1530 PDF
Williams EJ, Fischer DP, England GCW, Dobson H, Pfeiffer DU, Sheldon IM, 2005 Clinical evaluation of postpartum vaginal mucus reflects uterine bacterial infection and the inflammatory response to endometritis in cattle. Theriogenology 63:102-117
Whiteford LC, Sheldon IM, 2005 Association between clinical hypocalcaemia and postpartum endometritis. Veterinary Record I157:202-204
Nash DM, Lane EA, Sheldon IM, 2005 The effect of semen on the in vitro inflammatory response by equine endometrium. Reproduction in Domestic Animals 40:343
Sheldon IM, Rycroft AN, Zhou C, 2004 Association between postpartum pyrexia and uterine bacterial infection in dairy cattle. Veterinary Record 154:289-293
von Heimendahl A, Sheldon IM, England GCW, 2004 Influence of Griseofulvin treatment on semen quality in the dog. Animal Reproduction Science 80:175-181
Sheldon IM, Noakes DE, Rycroft AN, Dobson H, 2004 Effect of intrauterine administration of oestradiol on postpartum uterine bacterial infection in cattle. Animal Reproduction Science 81:13-23
Sheldon IM, Bushnell M, Montgomery J, Rycroft AN, 2004 Minimum inhibitory concentrations of some antimicrobial drugs against bacteria causing uterine infections in cattle. Veterinary Record 155:383-387
Sheldon IM. 2004 The postpartum uterus. Vet Clin North Am Food Anim Pract. 20(3):569-91. Review.
Sheldon IM, Dobson H. 2004 Postpartum uterine health in cattle. Anim Reprod Sci. 82-83:295-306. Review.
Sheldon IM, Noakes DE, Rycroft AN, Dobson H, 2003 The effect of intrauterine administration of estradiol on postpartum uterine involution in cattle.Theriogenology 59:1357-1371
Sheldon IM, Noakes DE, Bayliss M, Dobson H, 2003 The effect of oestradiol on postpartum uterine involution in sheep. Animal Reproduction Science 78:57-70
Sheldon IM, Dobson H. 2003 Reproductive challenges facing the cattle industry at the beginning of the 21st century. Reproduction (Suppl.) 61:1-13. Review.
Sheldon IM, Barrett DC and Boyd H 2003 The postpartum period. In Bovine Medicine 2nd Edition. Editor: AH Andrews. Blackwell Publishing Ltd, Oxford. pp 508-529
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 123:837-845 Open PDF
Sheldon IM, Noakes DE, Dobson H, 2002 Effect of the regressing corpus luteum of pregnancy on ovarian folliculogenesis after parturition in cattle. Biology of Reproduction 66:266-271
Regassa, Sheldon I, Noakes DE, 2002 Effect of experimentally induced metritis on uterine involution, acute phase protein response and PGFM secretion in the postpartum ewe. Veterinary Record 150:605-607
Sheldon IM, Noakes DE, Rycroft AN, Dobson H, 2002 Effect of postpartum manual examination of the vagina on uterine bacterial contamination in cows.Veterinary Record 151:531-534
Sheldon IM 2002 Utero-ovarian signalling in the postpartum cow. PhD thesis, University of Liverpool
Sheldon IM, Noakes DE, Rycroft A, Dobson H 2001 Acute phase protein response to postpartum uterine bacterial contamination in cattle Veterinary Record 148, 172-175
Sheldon IM 2001 The caesarean operation and the surgical preparation of teaser males. Editors: David E. Noakes, Timothy J. Parkinson, Gary C.W. England: Arthur's Veterinary Reproduction and Obstetrics. London, WB Saunders. pp 341-365
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 Journal of Reproduction and Fertility 119, 157-163
Sheldon IM, Noakes DE and Dobson H 2000 The influence of ovarian activity and uterine involution determined by ultrasonography on subsequent reproductive performance Theriogenology 54, 409-419
Subandrio AL, Sheldon IM and Noakes DE 2000 Peripheral and intrauterine neutrophil function in the cow: the influence of endogenous and exogenous sex steroid hormones Theriogenology 53 1591-1608
Sheldon IM and Noakes DE 1998 Comparison of three treatments for bovine endometritis Veterinary Record 142 575-9
Sheldon IM 1997 Bovine fertility - practical implications of the maternal recognition of pregnancy In Practice 19 546-556
Sheldon IM 1995 Suspected venereal spread of Corynebacterium renale Veterinary Record 137 100
Sheldon IM 1995 A case of iatrogenic reticulitis Veterinary Record 136 126
Sheldon IM 1994)A field case of granulocytopenic disease of calves Veterinary Record 135 408
Sheldon IM 1994 Clinical effects of buserelin on pregnancy rates in cattle Bovine Practitioner 28 106-108
Sheldon IM 1994 Digital and interdigital dermatitis in dairy cattle. Veterinary Record 134 559-60
Sheldon IM and Dobson H 1993 Effects of gonadotrophin releasing hormone administered 11 days after insemination on the pregnancy rates of cattle to the first and later services. Veterinary Record 133, 160-163
Book chapters
Sheldon IM 2018 Chapter 23: The Metritis Complex in Cattle. Editors: David E. Noakes, Timothy J. Parkinson, Gary C.W. England, Veterinary Reproduction & Obstetrics 10th Edition, WB Saunders. ISBN 9780702072338, 408-433, DOI 10.1016/B978-0-7020-7233-8.00023-9.
Sheldon IM, Price JC, Turner ML, Bromfield JJ, Cronin JJ 2014 Uterine infection and immunity in cattle. In “Reproduction in Domestic Ruminants VIII”, pp 415-430. Editors: Juengel JJ, Miyamoto A, Price C, Reynolds LP, Smith MF, Webb R. Published by Context Products Ltd, Ashby de la Zouch, UK.
Sheldon IM, Barrett DC and Boyd H 2003 The postpartum period. In Bovine Medicine 2nd Edition. Editor: AH Andrews. Blackwell Publishing Ltd, Oxford. pp 508-529
Sheldon IM 2002 Reproductive challenges facing the cattle industry at the beginning of the 21st century. In Reproduction in Domestic Ruminants V. Cambridge, SRF. pp 1-13
Sheldon IM 2001 The caesarean operation and the surgical preparation of teaser males. Editors: David E. Noakes, Timothy J. Parkinson, Gary C.W. England: Arthur's Veterinary Reproduction and Obstetrics. London, WB Saunders. pp 341-365
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