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

Mammalian reproductive physiology and the development of viviparity co-evolved with inflammation and immunity over millennia. Many inflammatory mediators contribute to paracrine and endocrine signalling, and the maintenance of tissue homeostasis in the female reproductive tract. However, inflammation is also a feature of microbial infections of the reproductive tract. Bacteria and viruses commonly cause endometritis, perturb ovarian follicle development and suppress the endocrine activity of the hypothalamus and pituitary in cattle. Innate immunity is an evolutionary ancient system that orchestrates host cell inflammatory responses aimed at eliminating pathogens and repairing damaged tissue. Pattern recognition receptors on host cells bind pathogen-associated molecular patterns and damage-associated molecular patterns, leading to the activation of intracellular MAPK and NFκB signalling pathways and the release of inflammatory mediators. Inflammatory mediators typically include the interleukin cytokines IL1β and IL6, chemokines such as IL8, interferons and prostaglandins. This review outlines the mechanisms of inflammation and innate immunity in the bovine female reproductive tract during health and disease condition.

[1]  K. Okuda,et al.  Inter- and intra-cellular mechanisms of prostaglandin F2alpha action during corpus luteum regression in cattle. , 2019, Society of Reproduction and Fertility supplement.

[2]  H. Henderson,et al.  Influence of pathogenic bacteria species present in the postpartum bovine uterus on proteome profiles. , 2015, Reproduction, fertility, and development.

[3]  O. Sandra,et al.  Differential Endometrial Cell Sensitivity to a Cholesterol-Dependent Cytolysin Links Trueperella pyogenes to Uterine Disease in Cattle1 , 2014, Biology of reproduction.

[4]  R. Kowsar,et al.  Bovine oviduct epithelial cells downregulate phagocytosis of sperm by neutrophils: prostaglandin E2 as a major physiological regulator. , 2014, Reproduction.

[5]  I. M. Sheldon,et al.  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 , 2014, Endocrinology.

[6]  I. M. Sheldon,et al.  Granulosa Cells from Emerged Antral Follicles of the Bovine Ovary Initiate Inflammation in Response to Bacterial Pathogen-Associated Molecular Patterns via Toll-Like Receptor Pathways1 , 2013, Biology of reproduction.

[7]  J. Bromfield,et al.  Pathogen-associated molecular patterns initiate inflammation and perturb the endocrine function of bovine granulosa cells from ovarian dominant follicles via TLR2 and TLR4 pathways. , 2013, Endocrinology.

[8]  Takashi Shimizu,et al.  Regulation of Innate Immune Function in Bovine Oviduct Epithelial Cells in Culture: The Homeostatic Role of Epithelial Cells in Balancing Th1/Th2 Response , 2013, The Journal of reproduction and development.

[9]  M. Goldberg,et al.  Bacterial Subversion of Host Innate Immune Pathways , 2013, Science.

[10]  T. Misztal,et al.  The effect of rivastigmine on the LPS-induced suppression of GnRH/LH secretion during the follicular phase of the estrous cycle in ewes. , 2013, Animal reproduction science.

[11]  T. Spencer,et al.  Physiology and Endocrinology Symposium: biological role of interferon tau in endometrial function and conceptus elongation. , 2013, Journal of animal science.

[12]  J. Bromfield,et al.  Lipopolysaccharide Reduces the Primordial Follicle Pool in the Bovine Ovarian Cortex Ex Vivo and in the Murine Ovary In Vivo1 , 2013, Biology of reproduction.

[13]  A. Herman,et al.  Immune stress up regulates TLR4 and Tollip gene expression in the hypothalamus of ewe. , 2013 .

[14]  J. Routly,et al.  Kisspeptin, c-Fos and CRFR type 2 expression in the preoptic area and mediobasal hypothalamus during the follicular phase of intact ewes, and alteration after LPS , 2013, Physiology & Behavior.

[15]  J. Patton,et al.  Influence of energy balance on the antimicrobial peptides S100A8 and S100A9 in the endometrium of the post-partum dairy cow , 2013, Reproduction.

[16]  K. Meade,et al.  Endometrial epithelial cells are potent producers of tracheal antimicrobial peptide and serum amyloid A3 gene expression in response to E. coli stimulation. , 2013, Veterinary immunology and immunopathology.

[17]  R. Bicalho,et al.  Diversity and Succession of Bacterial Communities in the Uterine Fluid of Postpartum Metritic, Endometritic and Healthy Dairy Cows , 2012, PloS one.

[18]  K. Meade,et al.  The postpartum endometrial inflammatory response: a normal physiological event with potential implications for bovine fertility. , 2012, Reproduction, fertility, and development.

[19]  I. M. Sheldon,et al.  Immunity and inflammation in the uterus. , 2012, Reproduction in domestic animals = Zuchthygiene.

[20]  I. M. Sheldon,et al.  Explants of Intact Endometrium to Model Bovine Innate Immunity and Inflammation Ex Vivo , 2012, American journal of reproductive immunology.

[21]  J. Magarian Blander,et al.  Beyond pattern recognition: five immune checkpoints for scaling the microbial threat , 2012, Nature Reviews Immunology.

[22]  T. Misztal,et al.  Central injection of exogenous IL-1β in the control activities of hypothalamic-pituitary-gonadal axis in anestrous ewes. , 2012, Reproduction in domestic animals = Zuchthygiene.

[23]  J. Routly,et al.  Estrous behavior, luteinizing hormone and estradiol profiles of intact ewes treated with insulin or endotoxin , 2012, Physiology & Behavior.

[24]  J. Routly,et al.  Effects of stress on reproduction in ewes. , 2012, Animal reproduction science.

[25]  F. Ceciliani,et al.  Widespread expression of SAA and Hp RNA in bovine tissues after evaluation of suitable reference genes. , 2012, Veterinary immunology and immunopathology.

[26]  Takashi Shimizu,et al.  Possible involvement of IFNT in lymphangiogenesis in the corpus luteum during the maternal recognition period in the cow. , 2011, Reproduction.

[27]  J. Bromfield,et al.  Lipopolysaccharide initiates inflammation in bovine granulosa cells via the TLR4 pathway and perturbs oocyte meiotic progression in vitro. , 2011, Endocrinology.

[28]  Takashi Shimizu,et al.  Evidence that polymorphonuclear neutrophils infiltrate into the developing corpus luteum and promote angiogenesis with interleukin-8 in the cow , 2011, Reproductive biology and endocrinology : RB&E.

[29]  R. Einspanier,et al.  Time-dependent mRNA expression of selected pro-inflammatory factors in the endometrium of primiparous cows postpartum , 2010, Reproductive biology and endocrinology : RB&E.

[30]  Grace Y Chen,et al.  Sterile inflammation: sensing and reacting to damage , 2010, Nature Reviews Immunology.

[31]  H. Dobson,et al.  Integration between different hypothalamic nuclei involved in stress and GnRH secretion in the ewe. , 2010, Reproduction in domestic animals = Zuchthygiene.

[32]  W. Heuwieser,et al.  A clinical approach to determine false positive findings of clinical endometritis by vaginoscopy by the use of uterine bacteriology and cytology in dairy cows. , 2010, Theriogenology.

[33]  P. Gajer,et al.  Vaginal microbiome of reproductive-age women , 2010, Proceedings of the National Academy of Sciences.

[34]  S. Han,et al.  Somatostatin inhibition of gonadotropin-releasing hormone neurons in female and male mice. , 2010, Endocrinology.

[35]  R. Einspanier,et al.  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. , 2010, Reproduction, fertility, and development.

[36]  S. Akira,et al.  Pattern Recognition Receptors and Inflammation , 2010, Cell.

[37]  J. Bromfield,et al.  Specific Strains of Escherichia coli Are Pathogenic for the Endometrium of Cattle and Cause Pelvic Inflammatory Disease in Cattle and Mice , 2010, PloS one.

[38]  J. Norman,et al.  Inflammatory pathways in female reproductive health and disease. , 2009, Reproduction.

[39]  P. Hansen,et al.  Phenotypic characterization of macrophages in the endometrium of the pregnant cow. , 2009, American journal of reproductive immunology.

[40]  H. Fan,et al.  Interleukin-6: an autocrine regulator of the mouse cumulus cell-oocyte complex expansion process. , 2009, Endocrinology.

[41]  J. Patton,et al.  Negative energy balance alters global gene expression and immune responses in the uterus of postpartum dairy cows , 2009, Physiological genomics.

[42]  R. Einspanier,et al.  Endometrial expression of selected transcripts involved in prostaglandin synthesis in cows with endometritis. , 2009, Theriogenology.

[43]  B. Beutler.  TLRs and innate immunity. , 2009, Blood.

[44]  R. S. Conlan,et al.  Toll-like receptor and antimicrobial peptide expression in the bovine endometrium , 2008, Reproductive biology and endocrinology : RB&E.

[45]  G. Leitner,et al.  Exposure to endotoxin during estrus alters the timing of ovulation and hormonal concentrations in cows. , 2008, Theriogenology.

[46]  Zhilin Liu,et al.  Immune-like mechanisms in ovulation , 2008, Trends in Endocrinology & Metabolism.

[47]  R. Medzhitov.  Origin and physiological roles of inflammation , 2008, Nature.

[48]  T. Okazaki,et al.  Hyaluronan fragments generated by sperm-secreted hyaluronidase stimulate cytokine/chemokine production via the TLR2 and TLR4 pathway in cumulus cells of ovulated COCs, which may enhance fertilization , 2008, Development.

[49]  G. Mor.  Inflammation and Pregnancy , 2008, Annals of the New York Academy of Sciences.

[50]  A. Cooney,et al.  Oocyte-Specific Deletion of Pten Causes Premature Activation of the Primordial Follicle Pool , 2008, Science.

[51]  C. Dinarello.  Historical insights into cytokines , 2007, European journal of immunology.

[52]  H. Dobson,et al.  Ovarian follicular cells have innate immune capabilities that modulate their endocrine function , 2007, Reproduction.

[53]  S. Cavirani,et al.  Bovine herpesvirus 4 is tropic for bovine endometrial cells and modulates endocrine function. , 2007, Reproduction.

[54]  I. M. Sheldon,et al.  Defining postpartum uterine disease in cattle. , 2006, Theriogenology.

[55]  B. Berisha,et al.  Changes in fibroblast growth factor 2 and its receptors in bovine follicles before and after GnRH application and after ovulation. , 2006, Reproduction.

[56]  H. S. Warren,et al.  Toll-like receptors. , 2005, Critical care medicine.

[57]  S. J. Billington,et al.  Arcanobacterium pyogenes: molecular pathogenesis of an animal opportunist , 2005, Antonie van Leeuwenhoek.

[58]  M. Miyoshi,et al.  Specific localization of macrophages in pregnant bovine caruncles. , 2004, Reproduction in domestic animals = Zuchthygiene.

[59]  R. DePinho,et al.  Suppression of Ovarian Follicle Activation in Mice by the Transcription Factor Foxo3a , 2003, Science.

[60]  H. Dobson,et al.  Influence of uterine bacterial contamination after parturition on ovarian dominant follicle selection and follicle growth and function in cattle. , 2002, Reproduction.

[61]  T. Iwanaga,et al.  Reduced phagocytotic activity of macrophages in the bovine retained placenta. , 2002, Reproduction in domestic animals = Zuchthygiene.

[62]  F. Karsch,et al.  Mechanisms for Ovarian Cycle Disruption by Immune/inflammatory Stress , 2002, Stress.

[63]  K. Yoshioka,et al.  Endotoxin induces delayed ovulation following endocrine aberration during the proestrous phase in Holstein heifers. , 2001, Domestic animal endocrinology.

[64]  H. Dobson,et al.  Acute phase protein responses to uterine bacterial contamination in caftle after calving , 2001, Veterinary Record.

[65]  R. Price,et al.  MUC1/episialin: a critical barrier in the female reproductive tract. , 2000, Journal of reproductive immunology.

[66]  A. Kruif,et al.  Risk factors for post partum ovarian dysfunction in high producing dairy cows in Belgium: a field study. , 2000, Theriogenology.

[67]  R. Corbeil,et al.  Immune and inflammatory responses to reproductive tract infection with Tritrichomonas foetus in immunized and control heifers. , 1996, The Journal of parasitology.

[68]  M. Ulstein,et al.  Identification of the Complement Regulatory Proteins CD46, CD55, and CD59 in Human Fallopian Tube, Endometrium, and Cervical Mucosa and Secretion , 1995, American journal of reproductive immunology.

[69]  G. Perez,et al.  Opioid peptides involvement in endotoxin-induced suppression of LH secretion in ovariectomized Holstein heifers. , 1995, Reproductive toxicology.

[70]  K. Kendrick,et al.  Increased body temperature, cortisol secretion, and hypothalamic expression of c-fos, corticotrophin releasing hormone and interleukin-1 beta mRNAs, following central administration of interleukin-1 beta in the sheep. , 1995, Brain research. Molecular brain research.

[71]  V. Gannon,et al.  Endometrial biopsy in Holstein-Friesian dairy cows. III. Bacteriological analysis and correlations with histological findings. , 1991, Canadian journal of veterinary research = Revue canadienne de recherche veterinaire.

[72]  R. Dedecker,et al.  Suppression of preovulatory luteinizing hormone surges in heifers after intrauterine infusions of Escherichia coli endotoxin. , 1989, American journal of veterinary research.

[73]  W. Adney,et al.  Aspects of bacteriology and endocrinology of cows with pyometra and retained fetal membranes. , 1984, American journal of veterinary research.

[74]  L. S. Leshin,et al.  Bacteremia-induced changes in pituitary hormone release and effect of naloxone. , 1984, The American journal of physiology.

[75]  D. Noakes,et al.  Effects of exogenous oestrogen and experimentally induced endometritis on absorption of sodium benzylpenicillin from the cow's uterus , 1982, Veterinary Record.

[76]  L. Espey.  Ovulation as an inflammatory reaction--a hypothesis. , 1980, Biology of reproduction.

[77]  L. Rowson,et al.  Influence of Ovarian Hormones on Uterine Infection , 1953, Nature.

[78]  J. Kagan,et al.  The Dorsoventral Regulatory Gene Cassette spätzle / Toll / cactus Controls the Potent Antifungal Response in Drosophila Adults , 2015 .

[79]  I. M. Sheldon,et al.  Polarised bovine endometrial epithelial cells vectorially secrete prostaglandins and chemotactic factors under physiological and pathological conditions. , 2013, Reproduction.

[80]  R. Wanke,et al.  Gene expression profiling of bovine peripartal placentomes: detection of molecular pathways potentially involved in the release of foetal membranes. , 2012, Reproduction.

[81]  J. Tschopp,et al.  The Inflammasomes , 2010, Cell.

[82]  H. Dobson,et al.  Bacterial lipopolysaccharide induces an endocrine switch from prostaglandin F2alpha to prostaglandin E2 in bovine endometrium. , 2009, Endocrinology.

[83]  H. Dobson,et al.  Expression and function of Toll-like receptor 4 in the endometrial cells of the uterus. , 2006, Endocrinology.

[84]  E. Keeffe,et al.  Annals of Clinical Microbiology and Anti microbials , 2005 .

[85]  F. Karsch,et al.  Endotoxin inhibits the surge secretion of gonadotropin-releasing hormone via a prostaglandin-independent pathway. , 2004, Endocrinology.

[86]  L. Moreland.  Acute phase protein , 2004 .

[87]  S. Ochsner,et al.  Ovulation: new dimensions and new regulators of the inflammatory-like response. , 2002, Annual review of physiology.

[88]  B. Berisha,et al.  Stimulatory and synergistic effects of luteinising hormone and insulin like growth factor 1 on the secretion of vascular endothelial growth factor and progesterone of cultured bovine granulosa cells. , 2001, Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association.

[89]  M. Skinner,et al.  Kit-ligand/stem cell factor induces primordial follicle development and initiates folliculogenesis. , 1999, Endocrinology.

[90]  The leishmaniases in biology , 1987 .