Animal Reproduction (AR)
Animal Reproduction (AR)

Conceptus-modulated innate immune function during early pregnancy in ruminants: a review

Cecilia Constantino Rocha; Juliano Coelho da Silveira; Niamh Forde; Mario Binelli; Guilherme Pugliesi

Downloads: 1
Views: 634


Abstract: This review focuses on the innate immune events modulated by conceptus signaling during early pregnancy in ruminants. Interferon-tau (IFN-τ) plays a role in the recognition of pregnancy in ruminants, which involves more than the inhibition of luteolytic pulses of PGF2α to maintain corpus luteum function. For successful pregnancy establishment, the allogenic conceptus needs to prevent rejection by the female. Therefore, IFN-τ exerts paracrine and endocrine actions to regulate the innate immune system and prevent conceptus rejection. Additionally, other immune regulators work in parallel with IFN-τ, such as the pattern recognition receptors (PRR). These receptors are activated during viral and bacterial infections and in early pregnancy, but it remains unknown whether PPR expression and function are controlled by IFN-τ. Therefore, this review focuses on the main components of the innate immune response that are involved with early pregnancy and their importance to avoid conceptus rejection.


Interferon-tau, Toll-like receptors, Nod-like receptors, interleukins, luteolysis


Agod Z, Fekete T, Budai MM, Varga A, Szabo A, Moon H, Boldogh I, Biro T, Lanyi A, Bacsi A, Pazmandi K. Regulation of type I interferon responses by mitochondria-derived reactive oxygen species in plasmacytoid dendritic cells. Redox Biol. 2017;13:633-45. PMid:28818792.

Antoniazzi AQ, Webb BT, Romero JJ, Ashley RL, Smirnova NP, Henkes LE, Bott RC, Oliveira JF, Niswender GD, Bazer FW, Hansen TR. Endocrine delivery of interferon Tau protects the corpus Luteum from Prostaglandin F2 Alpha-Induced Luteolysis in Ewes1. Biol Reprod. 2013;88(6):88. PMid:23616594.

Bainbridge DR, Sargent IL, Ellis SA. Increased expression of major histocompatibility complex (MHC) class I transplantation antigens in bovine trophoblast cells before fusion with maternal cells. Reproduction. 2001;122(6):907-13. PMid:11732986.

Balloy V, Sallenave JM, Wu YZ, Touqui L, Latge JP, Si-Tahar M, Chignard M. Aspergillus fumigatus-induced Interleukin-8 Synthesis by Respiratory Epithelial Cells Is Controlled by the Phosphatidylinositol 3-Kinase, p38 MAPK, and ERK1/2 Pathways and not by the Toll-like Receptor-MyD88 Pathway. J Biol Chem. 2008;283(45):30513-21. PMid:18703508.

Banu SK, Lee J, Satterfield MC, Spencer TE, Bazer FW, Arosh JA. Molecular cloning and characterization of prostaglandin (PG) transporter in ovine endometrium: role for multiple cell signaling pathways in transport of PGF2alpha. Endocrinology. 2008;149(1):219-31. PMid:17901226.

Baruselli PS, Ferreira RM, Colli MHA, Elliff FM, Sa MF, Vieira L, de Freitas BG. Timed artificial insemination: current challenges and recent advances in reproductive efficiency in beef and dairy herds in Brazil. Anim Reprod. 2017;14:558-71.

Bazer FW, Spencer TE, Johnson GA. Interferons and Uterine receptivity. Semin Reprod Med. 2009;27(1):90-102. PMid:19197808.

Berkowitz RS, Hill JA, Kurtz CB, Anderson DJ. Effects of products of activated leukocytes (lymphokines and monokines) on the growth of malignant trophoblast cells in vitro. Am J Obstet Gynecol. 1988;158(1):199-203. PMid:2447775.

Binelli M, Subramaniam P, Diaz T, Johnson GA, Hansen TR, Badinga L, Thatcher WW. Bovine interferon-tau stimulates the Janus kinase-signal transducer and activator of transcription pathway in bovine endometrial epithelial cells. Biol Reprod. 2001;64(2):654-65. PMid:11159370.

Bott RC, Ashley RL, Henkes LE, Antoniazzi AQ, Bruemmer JE, Niswender GD, Bazer FW, Spencer TE, Smirnova NP, Anthony RV, Hansen TR. Uterine vein infusion of interferon tau (IFNT) extends luteal life span in ewes. Biol Reprod. 2010;82(4):725-35. PMid:20042537.

Bridi A, Bertolin K, Rissi VB, Mujica LKS, Glanzner WG, Macedo MP, Comim FV, Gonçalves PBD, Antoniazzi AQ. Parthenogenetic bovine embryos secrete type I interferon capable of stimulating ISG15 in luteal cell culture. Anim Reprod. 2018;15(4):1268-77.

Brooks K, Spencer TE. Biological Roles of Interferon Tau (IFNT) and Type I IFN Receptors in elongation of the ovine conceptus. Biol Reprod. 2015;92(2):10. PMid:25505203.

Calle A, Gutiérrez-Reinoso MÁ, Re M, Blanco J, De la Fuente J, Monguió-Tortajada M, Borràs FE, Yáñez-Mó M, Ramírez MÁ. Bovine peripheral blood MSCs chemotax towards inflammation and embryo implantation stimuli. J Cell Physiol. 2021;236(2):1054-67. PMid:32617972.

Calle A, López-Martín S, Monguió-Tortajada M, Borràs FE, Yáñez-Mó M, Ramírez MÁ. Bovine endometrial MSC: mesenchymal to epithelial transition during luteolysis and tropism to implantation niche for immunomodulation. Stem Cell Res Ther. 2019;10(1):23. PMid:30635057.

Choi Y, Johnson GA, Burghardt RC, Berghman LR, Joyce MM, Taylor KM, David Stewart M, Bazer FW, Spencer TE. Interferon regulatory factor-two restricts expression of interferon-stimulated genes to the endometrial stroma and glandular Epithelium of the Ovine Uterus1. Biol Reprod. 2001;65(4):1038-49. PMid:11566724.

Choi Y, Johnson GA, Spencer TE, Bazer FW. Pregnancy and interferon tau regulate major histocompatibility complex class I and beta2-microglobulin expression in the ovine uterus. Biol Reprod. 2003;68(5):1703-10. PMid:12606392.

Coutermarsh-Ott S, Eden K, Allen IC. Beyond the inflammasome: regulatory NOD-like receptor modulation of the host immune response following virus exposure. J Gen Virol. 2016;97(4):825-38. PMid:26763980.

Dai C, Sun L, Yu L, Zhu G, Wu S, Bao W. Effects of porcine MyD88 knockdown on the expression of TLR4 pathway-related genes and proinflammatory cytokines. Biosci Rep. 2016;36(6):e00409. PMid:27707937.

Davies CJ, Fisher PJ, Schlafer DH. Temporal and regional regulation of major histocompatibility complex Class I Expression at the Bovine Uterine/Placental Interface. Placenta. 2000;21(2-3):194-202. PMid:10736242.

Diskin MG, Sreenan JM. Fertilization and embryonic mortality-rates in beef heifers after artificial-insemination. J Reprod Fertil. 1980;59(2):463-8. PMid:7431304.

Doyle J, Ellis SA, O’Gorman GM, Aparicio Donoso IM, Lonergan P, Fair T. Classical and non-classical Major Histocompatibility Complex class I gene expression in in vitro derived bovine embryos. J Reprod Immunol. 2009;82(1):48-56. PMid:19682752.

Ezz MA, Marey MA, Elweza AE, Kawai T, Heppelmann M, Pfarrer C, Balboula AZ, Montaser A, Imakawa K, Zaabel SM, Shimada M, Miyamoto A. TLR2/4 signaling pathway mediates sperm-induced inflammation in bovine endometrial epithelial cells in vitro. PLoS One. 2019;14(4):e0214516. PMid:30995239.

Fair T. The contribution of the maternal immune system to the establishment of pregnancy in cattle. Front Immunol. 2015;6:8. PMid:25674085.

Fair T, Gutierrez-Adan A, Murphy M, Rizos D, Martin F, Boland MP, Lonergan P. Search for the bovine homolog of the murine ped gene and characterization of its messenger RNA expression during bovine preimplantation development. Biol Reprod. 2004;70(2):488-94. PMid:14568917.

Fekete T, Bencze D, Szabo A, Csoma E, Biro T, Bacsi A, Pazmandi K. Regulatory NLRs Control the RLR-Mediated Type I interferon and inflammatory responses in human dendritic cells. Front Immunol. 2018;9:19. PMid:30344524.

Forde N, Duffy GB, McGettigan PA, Browne JA, Mehta JP, Kelly AK, Mansouri-Attia N, Sandra O, Loftus BJ, Crowe MA, Fair T, Roche JF, Lonergan P, Evans ACO. Evidence for an early endometrial response to pregnancy in cattle: both dependent upon and independent of interferon tau. Physiol Genomics. 2012;44(16):799-810. PMid:22759920.

Forde N, Lonergan P. Transcriptomic analysis of the bovine endometrium: what is required to establish uterine receptivity to implantation in cattle? J Reprod Dev. 2012;58(2):189-95. PMid:22738902.

Forde N, Lonergan P. Interferon-tau and fertility in ruminants. Reproduction. 2017;154(5):F33-43. PMid:28887326.

Gifford CA, Racicot K, Clark DS, Austin KJ, Hansen TR, Lucy MC, Davies CJ, Ott TL. Regulation of interferon-stimulated genes in peripheral blood leukocytes in pregnant and bred, nonpregnant dairy cows. J Dairy Sci. 2007;90(1):274-80. PMid:17183095.

Green JC, Okamura CS, Poock SE, Lucy MC. Measurement of interferon-tau (IFN-τ) stimulated gene expression in blood leukocytes for pregnancy diagnosis within 18–20d after insemination in dairy cattle. Anim Reprod Sci. 2010;121(1-2):24-33. PMid:20554404.

Hansen PJ. Regulation of immune cells in the uterus during pregnancy in ruminants1. J Anim Sci. 2007;85(13, Suppl.):E30-1. PMid:17322123.

Hansen PJ, Bazer FW, Segerson EC Jr. Skin graft survival in the uterine lumen of ewes treated with progesterone. Am J Reprod Immunol Microbiol. 1986;12(2):48-54. PMid:3538916.

Hansen TR, Sinedino LDP, Spencer TE. Paracrine and endocrine actions of interferon tau (IFNT). Reproduction. 2017;154(5):F45-59. PMid:28982937.

Henkes LE, Pru JK, Ashley RL, Anthony RV, Veeramachaneni DNR, Gates KC, Hansen TR. Embryo Mortality in Isg15(-/-) mice is exacerbated by environmental stress. Biol Reprod. 2015;92(2):10. PMid:25505199.

Hernandez-Ledezma JJ, Mathialagan N, Villanueva C, Sikes JD, Roberts RM. Expression of bovine trophoblast interferons by in vitro-derived blastocysts is correlated with their morphological quality and stage of development. Mol Reprod Dev. 1993;36(1):1-6. PMid:8398124.

Hoebe K, Janssen E, Beutler B. The interface between innate and adaptive immunity. Nat Immunol. 2004;5(10):971-4. PMid:15454919.

Hruz T, Laule O, Szabo G, Wessendorp F, Bleuler S, Oertle L, Widmayer P, Gruissem W, Zimmermann P. Genevestigator v3: a reference expression database for the meta-analysis of transcriptomes. Adv Bioinforma. 2008;2008:420747. PMid:19956698.

Hyungchul H, Kathleen JA, Lea AR, Thomas RH. Low blood ISG15 mRNA and progesterone levels are predictive of non-pregnant dairy cows. J Endocrinol. 2006;191(2):505-12. PMid:17088421.

Ideta A, Hayama K, Nakamura Y, Sakurai T, Tsuchiya K, Tanaka S, Yamaguchi T, Fujiwara H, Imakawa K, Aoyagi Y. Intrauterine administration of peripheral blood mononuclear cells enhances early development of the pre-implantation bovine embryo. Mol Reprod Dev. 2010;77(11):954-62. PMid:21104766.

Imakawa K, Bai R, Kusama K. Integration of molecules to construct the processes of conceptus implantation to the maternal endometrium. J Anim Sci. 2018;96(7):3009-21. PMid:29554266.

Johnson GA, Austin KJ, Collins AM, Murdoch WJ, Hansen TR. Endometrial ISG17 mRNA and a related mRNA are induced by interferon-tau and localized to glandular epithelial and stromal cells from pregnant cows. Endocrine. 1999;10(3):243-52. PMid:10484288.

Johnson GA, Joyce MM, Yankey SJ, Hansen TR, Ott TL. The Interferon Stimulated Genes (ISG) 17 and Mx have different temporal and spatial expression in the ovine uterus suggesting more complex regulation of the Mx gene. J Endocrinol. 2002;174(2):R7-r11. PMid:12176677.

Johnson GA, Stewart MD, Gray CA, Choi Y, Burghardt RC, Yu-Lee LY, Bazer FW, Spencer TE. Effects of the estrous cycle, pregnancy, and interferon tau on 2′,5′-oligoadenylate synthetase expression in the ovine uterus. Biol Reprod. 2001;64(5):1392-9. PMid:11319143.

Kamat MM, Vasudevan S, Maalouf SA, Townson DH, Pate JL, Ott TL. Changes in myeloid lineage cells in the uterus and peripheral blood of dairy heifers during early pregnancy1. Biol Reprod. 2016;95(3):95. PMid:27512154.

Kawai T, Akira S. Toll-like receptors and their crosstalk with other innate receptors in infection and immunity. Immunity. 2011;34(5):637-50. PMid:21616434.

Kaya MS, Kose M, Guzeloglu A, Kıyma Z, Atli MO. Early pregnancy-related changes in toll-like receptors expression in ovine trophoblasts and peripheral blood leukocytes. Theriogenology. 2017;93:40-5. PMid:28257865.

Kiyma Z, Kose M, Atli MO, Ozel C, Hitit M, Sen G, Kaya M, Kaya MS, Kurar E, Kayis SA, Guzeloglu A. Investigation of interferon-tau stimulated genes (ISGs) simultaneously in the endometrium, corpus luteum (CL) and peripheral blood leukocytes (PBLs) in the preluteolytic stage of early pregnancy in ewes. Small Rumin Res. 2016;140:1-6.

Kizaki K, Shichijo-Kizaki A, Furusawa T, Takahashi T, Hosoe M, Hashizume K. Differential neutrophil gene expression in early bovine pregnancy. Reprod Biol Endocrinol. 2013;11(1):10. PMid:23384108.

Kose M, Kaya MS, Aydilek N, Kucukaslan I, Bayril T, Bademkiran S, Kiyma Z, Ozyurtlu N, Kayis SA, Guzeloglu A, Atli MO. Expression profile of interferon tau–stimulated genes in ovine peripheral blood leukocytes during embryonic death. Theriogenology. 2016;85(6):1161-6. PMid:26748865.

Lee CS, Wooding FBP, Morgan G. Quantitative analysis throughout pregnancy of intraepithelial large granular and non-granular lymphocyte distributions in the synepitheliochorial placenta of the cow. Placenta. 1997;18(8):675-81. PMid:9364603.

Li J, Roberts RM. Structure-function relationships in the interferon-tau (IFN-tau). Changes in receptor binding and in antiviral and antiproliferative activities resulting from site-directed mutagenesis performed near the carboxyl terminus. J Biol Chem. 1994;269(40):24826-33. PMid:7929162.

Li T, Hai L, Liu B, Mao W, Liu K, Yuan S, Qian R, Guo Y, Jia Y, Bao H, Cao J, 2020. TLR2/4 promotes PGE2 production to increase tissue damage in Escherichia coli-infected bovine endometrial explants via MyD88/p38 MAPK pathway. Theriogenology. 152, 129-138.

Li, X.C., Zand, M.S., Li, Y., Zheng, X.X., Strom, T.B., 1998. On histocompatibility barriers, Th1 to Th2 immune deviation, and the nature of the allograft responses. Journal of immunology. 161, 2241-2247.

Lo WC, Summers PM. In vitro culture and interferon-tau secretion by ovine blastocysts. Anim Reprod Sci. 2002;70(3-4):191-202. PMid:11943489.

Loo Y-M, Gale M Jr. Immune Signaling by RIG-I-like Receptors. Immunity. 2011;34(5):680-92. PMid:21616437.

Maeda Y, Ohtsuka H, Tomioka M, Oikawa M. Effect of progesterone on Th1/Th2/Th17 and regulatory T cell-related genes in peripheral blood mononuclear cells during pregnancy in cows. Vet Res Commun. 2013;37(1):43-9. PMid:23203561.

Mann GE, Lamming GE. Relationship between maternal endocrine environment, early embryo development and inhibition of the luteolytic mechanism in cows. Reproduction. 2001;121(1):175-80. PMid:11226041.

Mansouri-Attia N, Oliveira LJ, Forde N, Fahey AG, Browne JA, Roche JF, Sandra O, Reinaud P, Lonergan P, Fair T. Pivotal role for monocytes/macrophages and dendritic cells in maternal immune response to the developing Embryo in Cattle1. Biol Reprod. 2012;87(5):87. PMid:23034158.

Matsuyama S, Kojima T, Kato S, Kimura K. Relationship between quantity of IFNT estimated by IFN-stimulated gene expression in peripheral blood mononuclear cells and bovine embryonic mortality after AI or ET. RB&E. 2012;10(1):21-21. PMid:22439976.

Medawar PB. Some immunological and endocrinological problems raised by evolution of viviparity in vertebrates. Symp. Soc. Exp. Biol. 1953;7:320-338.

Meeusen E, Bischof R, Lee CS. Comparative T-Cell responses during pregnancy in large animals and humans. Am. J. Reprod. Immunol. 2001;46:169-179.

Melo GD, Pinto LMF, Rocha CC, Motta IG, Silva LA, da Silveira JC, Gonella-Diaza AM, Binelli M, Pugliesi G. Type I interferon receptors and interferon-τ-stimulated genes in peripheral blood mononuclear cells and polymorphonuclear leucocytes during early pregnancy in beef heifers. Reprod Fertil Dev. 2020a;32(11):953-66. PMid:32646539.

Melo GD, Mello BP, Ferreira CA, Souto Godoy Filho CA, Rocha CC, Silva AG, Reese ST, Madureira EH, Pohler KG, Pugliesi G. Applied use of interferon-tau stimulated genes expression in polymorphonquclear cells to detect pregnancy compared to other early predictors in beef cattle. Theriogenology. 2020b

Meyer MD, Hansen PJ, Thatcher WW, Drost M, Badinga L, Roberts RM, Li J, Ott TL, Bazer FW. Extension of corpus luteum lifespan and reduction of uterine secretion of Prostaglandin F2α of Cows in response to recombinant Interferon-τ. J Dairy Sci. 1995;78(9):1921-31. PMid:8550901.

Meyerholz MM, Mense K, Knaack H, Sandra O, Schmicke M. Pregnancy-Induced ISG-15 and MX-1 Gene expression is detected in the liver of holstein–friesian heifers during late peri-implantation period. Reprod Domest Anim. 2015;51(1):175-7. PMid:26549692.

Mosmann TR, Cherwinski H, Bond MW, Giedlin MA, Coffman RL. Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J Immunol. 1986;136(7):2348-57. PMid:2419430.

Muñoz M, Corrales FJ, Caamaño JN, Díez C, Trigal B, Mora MI, Martín D, Carrocera S, Gómez E. Proteome of the early embryo–maternal dialogue in the cattle uterus. J Proteome Res. 2012;11(2):751-66. PMid:22148898.

Nakamura K, Kusama K, Bai R, Sakurai T, Isuzugawa K, Godkin JD, Suda Y, Imakawa K. Induction of IFNT-Stimulated genes by conceptus-derived exosomes during the attachment period. PLoS One. 2016;11(6):16. PMid:27351483.

Ock SA, Baregundi Subbarao R, Lee YM, Lee JH, Jeon RH, Lee SL, Park JK, Hwang SC, Rho GJ. Comparison of immunomodulation properties of porcine mesenchymal stromal/stem cells derived from the bone marrow, adipose tissue, and dermal skin tissue. Stem Cells Int. 2016;2016:9581350. PMid:26798368.

O’Gorman GM, Al Naib A, Ellis SA, Mamo S, O’Doherty AM, Lonergan P, Fair T. Regulation of a bovine nonclassical major histocompatibility complex class i gene promoter. Biol Reprod. 2010;83(2):296-306. PMid:20427761.

Oliveira JF, Henkes LE, Ashley RL, Purcell SH, Smirnova NP, Veeramachaneni DNR, Anthony RV, Hansen TR. Expression of Interferon (IFN)-Stimulated genes in extrauterine tissues during early pregnancy in sheep is the consequence of Endocrine IFN-τ Release from the Uterine Vein. Endocrinology. 2008;149(3):1252-9. PMid:18063687.

Ott TL. <em>Symposium review:</em> Immunological detection of the bovine conceptus during early pregnancy<sup>*</sup>. J Dairy Sci. 2019;102(4):3766-77. PMid:30712941.

Ott TL. Immunological detection of pregnancy: evidence for systemic immune modulation during early pregnancy in ruminants. Theriogenology. 2020;150:498-503. PMid:32331860.

Ott TL, Fleming JG, Spencer TE, Joyce MM, Chen P, Green CN, Zhu D, Welsh TH Jr, Harms PG, Bazer FW. Effects of exogenous recombinant ovine interferon tau on circulating concentrations of progesterone, cortisol, luteinizing hormone, and antiviral activity; interestrous interval; rectal temperature; and uterine response to oxytocin in cyclic ewes. Biol Reprod. 1997;57(3):621-9. PMid:9283000.

Ott TL, Kamat MM, Vasudevan S, Townson DH, Pate JL. Maternal immune responses to conceptus signals during early pregnancy in ruminants. Anim Reprod. 2014;11:237-45.

Oviedo-Boyso J, Bravo-Patino A, Baizabal-Aguirre VM. Collaborative action of Toll-like and NOD-like receptors as modulators of the inflammatory response to pathogenic bacteria. Mediators Inflamm. 2014;2014:432785. PMid:25525300.

Perez-Sepulveda A, Torres MJ, Khoury M, Illanes SE. Innate immune system and preeclampsia. Front Immunol. 2014;5:244. PMid:24904591.

Pugliesi, G., Miagawa, B.T., Paiva, Y.N., França, M.R., Silva, L.A., Binelli, M. Conceptus-induced changes in the gene expression of blood immune cells and the ultrasound-accessed luteal function in beef cattle: How early can we detect pregnancy? Biol. Reprod. 2014;91(4):1-12.

Rashid MB, Talukder AK, Kusama K, Haneda S, Takedomi T, Yoshino H, Moriyasu S, Matsui M, Shimada M, Imakawa K, Miyamoto A. Evidence that interferon-tau secreted from Day-7 embryo in vivo generates anti-inflammatory immune response in the bovine uterus. Biochem Biophys Res Commun. 2018;500(4):879-84. PMid:29702095.

Reese ST, Franco GA, Poole RK, Hood R, Fernadez Montero L, Oliveira Filho RV, Cooke RF, Pohler KG. Pregnancy loss in beef cattle: A meta-analysis. Anim Reprod Sci. 2020;212:11. PMid:31864492.

Rempel LA, Francis BR, Austin KJ, Hansen TR. Isolation and Sequence of an Interferon-τ-Inducible, Pregnancy- and Bovine Interferon-Stimulated Gene Product 15 (ISG15)-Specific, Bovine Ubiquitin-Activating E1-Like (UBE1L) Enzyme1. Biol Reprod. 2005;72(2):365-72. PMid:15385418.

Roberts RM, Chen Y, Ezashi T, Walker AM. Interferons and the maternal-conceptus dialog in mammals. Semin Cell Dev Biol. 2008;19(2):170-7. PMid:18032074.

Rocha CC, da Silva Andrade SC, de Melo GD, Motta IG, Coutinho LL, Gonella-Diaza AM, Binelli M, Pugliesi G. Early pregnancy-induced transcripts in peripheral blood immune cells in Bos indicus heifers. Sci Rep. 2020;10(1):13733. PMid:32792605.

Romero JJ, Antoniazzi AQ, Nett TM, Ashley RL, Webb BT, Smirnova NP, Bott RC, Bruemmer JE, Bazer FW, Anthony RV, Hansen TR. Temporal release, paracrine and endocrine actions of ovine conceptus-derived interferon-tau during early pregnancy. Biol Reprod. 2015;93(6):93. PMid:26559679.

Rosenfeld CS, Han C-S, Alexenko AP, Spencer TE, Roberts RM. Expression of Interferon Receptor Subunits, IFNAR1 and IFNAR2, in the Ovine Uterus1. Biol Reprod. 2002;67(3):847-53. PMid:12193393.

Ruhmann B, Giller K, Hankele AK, Ulbrich SE, Schmicke M. Interferon-tau induced gene expression in bovine hepatocytes during early pregnancy. Theriogenology. 2017;104:198-204. PMid:28888122.

Ruiz-Gonzalez I, Xu J, Wang XQ, Burghardt RC, Dunlap KA, Bazer FW. Exosomes, endogenous retroviruses and toll-like receptors: pregnancy recognition in ewes. Reproduction. 2015;149(3):281-91. PMid:25526899.

Sağsöz H, Akbalik ME, Saruhan BG, Ketani MA. Localization of estrogen receptor α and progesterone receptor B in bovine cervix and vagina during the follicular and luteal phases of the sexual cycle. Biotech Histochem. 2011;86(4):262-71. PMid:20438296.

Schalue-Francis TK, Farin PW, Cross JC, Keisler D, Roberts RM. Effect of injected bovine interferon-alpha I1 on estrous cycle length and pregnancy success in sheep. J Reprod Fertil. 1991;91(1):347-56. PMid:1995858.

Schroder K, Tschopp J. The inflammasomes. Cell. 2010;140(6):821-32. PMid:20303873.

Sena P, Riccio M, Marzona L, Nicoli A, Marsella T, Marmiroli S, Bertacchini J, Fano RA, La Sala GB, De Pol A. Human MATER localization in specific cell domains of oocytes and follicular cells. Reprod Biomed Online. 2009;18(2):226-34. PMid:19192343.

Shirasuna K, Matsumoto H, Kobayashi E, Nitta A, Haneda S, Matsui M, Kawashima C, Kida K, Shimizu T, Miyamoto A. Upreguliation of interferon-stimulated genes and Interleukin-10 in peripheral blood immune cells during early pregnancy in dairy cows. J Reprod Dev. 2012;58(1):84-90. PMid:22052007.

Silvia WJ, Niswender GD. Maintenance of the Corpus Luteum of Early Pregnancy in the Ewe. III. Differences between pregnant and nonpregnant ewes in luteal responsiveness to Prostaglandin F2α2. J Anim Sci. 1984;59(3):746-53. PMid:6593317.

Spencer TE, Becker WC, George P, Mirando MA, Ogle TF, Bazer FW. Ovine interferon-tau inhibits estrogen receptor up-regulation and estrogen-induced luteolysis in cyclic ewes. Endocrinology. 1995;136(11):4932-44. PMid:7588227.

Spencer TE, Johnson GA, Bazer FW, Burghardt RC. Fetal-maternal interactions during the establishment of pregnancy in ruminants. Soc Reprod Fertil Suppl. 2007;64(1):379-96. PMid:17491160.

Spencer TE, Ott TL, Bazer FW. Expression of interferon regulatory factors one and two in the ovine endometrium: effects of pregnancy and ovine interferon Tau1. Biol Reprod. 1998;58(5):1154-62. PMid:9603248.

Sponchiado M, Gomes NS, Fontes PK, Martins T, del Collado M, Pastore AD, Pugliesi G, Nogueira MFG, Binelli M. Pre-hatching embryo-dependent and -independent programming of endometrial function in cattle. PLoS One. 2017;12(4):23. PMid:28423001.

Stark GR, Kerr IM, Williams BRG, Silverman RH, Schreiber RD. How cells respond to interferons. Annu Rev Biochem. 1998;67(1):227-64. PMid:9759489.

Stevenson JL, Dalton JC, Ott TL, Racicot KE, Chebel RC. Correlation between reproductive status and steady-state messenger ribonucleic acid levels of the Myxovirus resistance gene, MX2, in peripheral blood leukocytes of dairy heifers1,2. J Anim Sci. 2007;85(9):2163-72. PMid:17431047.

Takino T, Okamura T, Ando T, Hagiwara K. Change in the responsiveness of interferon-stimulated genes during early pregnancy in cows with Borna virus-1 infection. BMC Vet Res. 2016;12(1):4. PMid:27842550.

Talukder AK, Rashid MB, Yousef MS, Kusama K, Shimizu T, Shimada M, Suarez SS, Imakawa K, Miyamoto A. Oviduct epithelium induces interferon-tau in bovine Day-4 embryos, which generates an anti-inflammatory response in immune cells. Sci Rep. 2018;8(1):7850. PMid:29777205.

Talukder AK, Yousef MS, Rashid MB, Awai K, Acosta TJ, Shimizu T, Okuda K, Shimada M, Imakawa K, Miyamoto A. Bovine embryo induces an anti-inflammatory response in uterine epithelial cells and immune cells in vitro: possible involvement of interferon tau as an intermediator. J Reprod Dev. 2017;63(4):425-34. PMid:28603222.

Thompson MR, Kaminski JJ, Kurt-Jones EA, Fitzgerald KA. Pattern recognition receptors and the innate immune response to viral infection. Viruses. 2011;3(6):920-40. PMid:21994762.

Tuo W, Brown WC, Roger E, Zhu D, Lin G, Smith R 3rd, Bazer FW. Trophoblast IFN-τ Differentially Induces Lymphopenia and Neutropenia in Lambs. J Interferon Cytokine Res. 1998;18(9):731-7. PMid:9781812.

Vasudevan S, Kamat MM, Walusimbi SS, Pate JL, Ott TL. Effects of early pregnancy on uterine lymphocytes and endometrial expression of immune-regulatory molecules in dairy heifers. Biol Reprod. 2017;97(1):104-18. PMid:28633489.

Velázquez MML, Peralta MB, Angeli E, Stassi AF, Gareis NC, Durante L, Cainelli S, Salvetti NR, Rey F, Ortega HH. Immune status during postpartum, peri-implantation and early pregnancy in cattle: an updated view. Anim Reprod Sci. 2019;206:1-10. PMid:31133358.

Wang PY, Han XH, Mo BW, Huang GJ, Wang CM. LPS enhances TLR4 expression and IFN-gamma production via the TLR4/IRAK/NF-kappa B signaling pathway in rat pulmonary arterial smooth muscle cells. Mol Med Rep. 2017;16(3):3111-6. PMid:28714001.

Wang XL, Wang K, Han GC, Zeng SM. A potential autocrine role for interferon tau in ovine trophectoderm. Reprod Domest Anim. 2013;48(5):819-25. PMid:23551360.

Wei XX, Li XZ, Zheng XC, Jia P, Wang JJ, Yang XL, Yu L, Shi XJ, Tong GX, Liu H. Toll-like receptors and interferon associated immune factors responses to spring viraemia of carp virus infection in common carp (Cyprinus carpio). Fish Shellfish Immunol. 2016;55:568-76. PMid:27263115.

Wiltbank MC, Baez GM, Garcia-Guerra A, Toledo MZ, Monteiro PL, Melo LF, Ochoa JC, Santos JE, Sartori R. Pivotal periods for pregnancy loss during the first trimester of gestation in lactating dairy cows. Theriogenology. 2016;86(1):239-53. PMid:27238438.

Wu X, Zang F, Liu M, Zhuo L, Wu J, Xia X, Feng Y, Yu R, Huang P, Yang S. Genetic variants in RIG-I-like receptor influences HCV clearance in Chinese Han population. Epidemiol Infect. 2019;147:e195. PMid:31364528.

Yang L, Wang XL, Wan PC, Zhang LY, Wu Y, Tang DW, Zeng SM. Up-regulation of expression of interferon-stimulated gene 15 in the bovine corpus luteum during early pregnancy. J Dairy Sci. 2010;93(3):1000-11. PMid:20172220.

Yang L, Yao XL, Li SJ, Chen K, Wang YX, Chen L, Zhang LY. Expression of genes associated with Luteolysis in Peripheral blood mononuclear cells during early pregnancy in cattle. Mol Reprod Dev. 2016;83(6):509-15. PMid:27061007.

Yankey SJ, Hicks BA, Carnahan KG, Assiri AM, Sinor SJ, Kodali K, Stellflug JN, Stellflug JN, Ott TL. Expression of the antiviral protein Mx in peripheral blood mononuclear cells of pregnant and bred, non-pregnant ewes. J Endocrinol. 2001;170(2):R7-11. PMid:11479146.

Zhang L, Xia Y, Tang F, Li SJ, Yang L, Wang B. The regulation of intrauterine immune cytokines and chemokines during early pregnancy in the bovine. Large Anim Rev. 2015;21:23-31.

Zhao J, Yu HY, Zhao Y, Li SQ, Fu XL, Zhou W, Xia BB, Wang ML, Chen J. Pharmacokinetics of the recombinant ovine interferon-tau in lambs. Pol J Vet Sci. 2019;22(1):75-82. PMid:30997764.

Submitted date:

Accepted date:

60953498a9539533a85d9426 animreprod Articles
Links & Downloads

Anim Reprod

Share this page
Page Sections