Parthenogenetic bovine embryos secrete type I interferon capable of stimulating ISG15 in luteal cell culture
Alessandra Bridi, Kalyne Bertolin, Vitor B. Rissi, Lady K.S. Mujica, Werner G. Glanzner, Mariana P. de Macedo, Fabio V. Comim, Paulo B.D. Gonçalves, Alfredo Q. Antoniazzi
Interferon tau (IFNT) is the pregnancy recognition signal in ruminants and is secreted by trophoblast cells. Paracrine action in the endometrium is well established by inhibiting luteolytic pulses of prostaglandin F2 alpha. Recently, endocrine action was documented in the corpus luteum, blood cell and liver. It was hypothesized that conditioned medium (CM) obtained from days 7, 9 and 12 parthenogenetic embryos alters luteal cell gene expression. The aim was to establish a bovine mixed luteal cell culture to evaluate cellular response associated to interferon stimulated genes, steroidogenesis and apoptosis. Conditioned medium was obtained from Days 7, 9 and 12 parthenogenetic (PA) embryos culture. Moreover, antiviral assay was performed on CM from Days 7, 9 and 12 to verify Type I interferon activity. Luteal cell culture was validated by steroidogenic and apoptotic genes (CYP11A1, HSD3B1, BAX, BCL2, AKT and XIAP mRNA expression), and concentration of progesterone as endpoint. Luteal cell culture was treated with interferon alpha (IFNA) and CM from parthenogenetic embryos. Antiviral assay revealed Type I interferon activity on CM from embryos increasing on Days 9 and 12. ISG15 mRNA was greater in the mixed luteal cells culture treated with 1, 10 and 100ng/ml of interferon alpha (IFNA) and also on Days 7, 9 and 12 CM treatments. Concentration of progesterone was not altered in luteal cell culture regardless of treatments. Steroidogenic and apoptotic genes were similar among groups in luteal cell culture treated with different doses of IFNA or CM from PA embryos. In conclusion, parthenogenetic embryo-derived CM has antiviral activity, luteal cell culture respond to Type I interferon by expressing IGS15. These data indicate this model can be used for IFNT endocrine signaling studies.
Adams JM, Cory S. 1998. The Bcl-2 protein family: arbiters of cell survival. Science, 281:1322-1326.
Antoniazzi AQ, Webb BT, Romero JJ, Ashley RL, Smirnova NP, Henkes LE, Bott RC, Oliveira JF, Niswende, GD, Bazer FW, Hansen TR. 2013. Endocrine delivery of interferon tau protects the corpus luteum from prostaglandin F2 alpha-induced luteolysis in ewes. Biol Reprod, 88:144.
Austin KJ, Ward SK, Teixeira MG, Dean VC, Moore DW, Hansen TR. 1996. Ubiquitin cross-reactive protein is released by the bovine uterus in response to interferon during early pregnancy. Biol Reprod, 54:600-606.
Austin KJ, Bany BM, Belden EL, Rempel LA, Cross JC, Hansen TR. 2003. Interferon-Stimulated Gene-15 (Isg15) Expression Is Up-Regulated in the Mouse Uterus in Response to the Implanting Conceptus. Endocrinology, 144:3107-3113.
Austin KJ, Carr AL, Pru JK, Hearne CE, George EL, Belden EL, Hansen TR. 2004. Localization of ISG15 and Conjugated Proteins in Bovine Endometrium Using Immunohistochemistry and Electron Microscopy. Endocrinology, 145, 967:975.
Bałakier H, Tarkowski AK. 1976. Diploid parthenogenetic mouse embryos produced by heat-shock and Cytochalasin B. J Embryol Exp Morphol, 35:25-39.
Bebington C, Doherty FJ, Fleming SD. 1999. Ubiquitin cross-reactive protein gene expression is increased in decidualized endometrial stromal cells at the initiation of pregnancy. Mol Hum Reprod, 5:966-972.
Bott RC, Ashley RL, Henkes LE, Antoniazzi AQ, Bruemmer JE, Niswender GD, Bazer FW, Spencer TE, Smirnova NP, Anthony RV, Hansen TR. 2010. Uterine vein infusion of interferon tau (IFNT) extends luteal life span in ewes. Biol Reprod, 82:725-735.
Brevini TAL, Gandolfi F. 2008. Parthenotes as a source of embryonic stem cells. Cell Proliferation, 41:20-30.
Gifford CA, Racicot K, Clark DS, Austin KJ, Hansen TR, Lucy MC, Davies CJ, Ott TL. 2007. Regulation of Interferon-Stimulated Genes in Peripheral Blood Leukocytes in Pregnant and Bred, Nonpregnant Dairy Cows. J Dairy Sci, 90:274-280.
Green MP, Spate LD, Bixby JA, Ealy AD, Roberts RM. 2005. A Comparison of the Anti-Luteolytic Activities of Recombinant Ovine Interferon-Alpha and -Tau in Sheep. Biol Reprod, 73:1087-1093.
Haas AL, Ahrens P, Bright PM, Ankel H. 1987. Interferon induces a 15-kilodalton protein exhibiting marked homology to ubiquitin. J Biol Chem, 262:11315-11323.
Han H, Austin KJ, Rempel LA, Hansen TR. 2006. Low blood ISG15 mRNA and progesterone levels are predictive of non-pregnant dairy cows. J Endocrinol, 191:505-512.
Henery CC, Kaufman MH. 1992. Cleavage rate of haploid and diploid parthenogenetic mouse embryos during the preimplantation period. Mol Reprod Dev, 31:258-263.
Imakawa K, Anthony RV, Kazemi M, Marotti KR, Polites HG, Roberts RM. 1987. Interferon-like sequence of ovine trophoblast protein secreted by embryonic trophectoderm. Nature, 330:377-379.
Loeb KR, Haas AL. 1992. The interferon-inducible 15-kDa ubiquitin homolog conjugates to intracellular proteins. J Biol Chem, 267:7806-7813.
Mann G, Lamming G. 2001. Relationship between maternal endocrine environment, early embryo development and inhibition of the luteolytic mechanism in cows. Reproduction, 121:175-180.
Manning BD, Cantley LC. 2007. AKT/PKB Signaling: Navigating Downstream. Cell, 129:1261-1274.
Méo SC, Yamazaki W, Ferreira CR, Perecin F, Saraiva NZ, Leal CLV, Garcia JM. 2007. Parthenogenetic activation of bovine oocytes using single and combined strontium, ionomycin and 6-dimethylaminopurine treatments. Zygote, 15:295-306.
Miyamoto Y, Skarzynski DJ, Okuda K. 2000. Is Tumor Necrosis Factor α a Trigger for the Initiation of Endometrial Prostaglandin F2α Release at Luteolysis in Cattle? Biol Reprod, 62:1109-1115.
Mogensen KE, Lewerenz M, Reboul J, Lutfalla G, Uzé G. 1999. The Type I Interferon Receptor: Structure, Function, and Evolution of a Family Business. J Interferon Cytokine Res, 19:1069-1098.
Narasimhan J, Potter JL, Haas AL. 1996. Conjugation of the 15-kDa Interferon-induced Ubiquitin Homolog Is Distinct from That of Ubiquitin. J Biol Chem, 271:324-330.
Niswender G. 2002. Molecular control of luteal secretion of progesterone. Reproduction, 123:333-339.
Oliveira JF, Henkes LE, Ashley RL, Purcell SH, Smirnova NP, Veeramachaneni DN, Anthony RV, Hansen TR. 2008. Expression of interferon (IFN)-stimulated genes in extrauterine tissues during early pregnancy in sheep is the consequence of endocrine IFN-tau release from the uterine vein. Endocrinology, 149:1252-1259.
Roberts RM, Chen Y, Ezashi T, Walker AM. 2008. Interferons and the maternal–conceptus dialog in mammals. Semin Cell Dev Biol, 19:170-177.
Roberts RM, Ealy AD, Alexenko AP, Han CS, Ezashi T. 1999. Trophoblast Interferons. Placenta, 20:259-264.
Shirasuna K, Matsumoto H, Matsuyama S, Kimura K, Bollwein H, Miyamoto A. 2015. Possible role of interferon tau on the bovine corpus luteum and neutrophils during the early pregnancy. Reproduction, 150:217-225.
Soloy E, Kanka J, Viuff D, Smith SD, Callesen H, Greve T. 1997. Time course of pronuclear deoxyribonucleic acid synthesis in parthenogenetically activated bovine oocytes. Biol Reprod, 57:27-35.
Subramaniam PS, Khan SA, Pontzer CH, Johnson HM. 1995. Differential recognition of the type I interferon receptor by interferons tau and alpha is responsible for their disparate cytotoxicities. Proc Natl Acad Sci U S A, 92:12270-12274.
Takahashi R, Deveraux Q, Tamm I, Welsh K, Assa-Munt N, Salvesen GS, Reed JC. 1998. A Single BIR Domain of XIAP Sufficient for Inhibiting Caspases. Journal of Biological Chemistry 273, 7787-7790.
Thatcher WW, Guzeloglu A, Mattos R, Binelli M, Hansen TR, Pru JK. 2001. Uterine-conceptus interactions and reproductive failure in cattle. Theriogenology, 56:1435-1450.
Vogel SN, Friedman RM, Hogan MM. 2001. Measurement of Antiviral Activity Induced by Interferons α, β, and. Curr Protoc Immunol, Chapter 6:Unit 6 9.
Yao N, Wan PC, Hao ZD, Gao FF, Yang L, Cui MS, Wu Y, Liu JH, Liu S, Chen H, Zeng SM. 2009. Expression of Interferon-tau mRNA in Bovine Embryos Derived from Different Procedures. Reprod Dom Anim, 44:132-139.