Animal Reproduction (AR)
Animal Reproduction (AR)
Original Article

Toll-like receptor 2 and 4 expression in the bovine corpus luteum during the different stages of the estrous cycle

Mehmet Osman Atli, Mehmet Köse, Mehmet Salih Kaya, Nurettin Aydilek, Aydin Güzeloğlu, Milo C. Wiltbank

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The aim of this study was to elucidate the presence of components of the innate immune system in the bovine corpus luteum (CL) by detecting the expression and cell-specific localization of TLR2 and TLR4 during different stages of the estrous cycle in a control study design. Bovine CL samples were collected from a local slaughterhouse and assigned to three groups as follows: developing CL (dCL; n = 6, approx. days 3–6), mature CL (mCL; n = 5, approx. days 8–12), and regressing CL (rCL; n = 5, approx. days 17–19). An upregulation of TLR2 mRNA was detected only in rCL (P < 0.05). Localization of the TLR2 protein was particularly apparent in luteal cells and a prominent immunofluorescent signal corresponding to TLR2 was detected only in rCL. TLR4 mRNA were higher in mCL and rCL compared to dCL (P < 0.05). The presence of the TLR4 protein in bovine CL was clearly detected in the luteal cells of both mCL and rCL. The results of this study suggest a role for TLRs in the development, maintenance, and regression of bovine CL. TLR signaling mediated pathway in luteal cells may involve in the regression of CL via regulation of TLR2 and TLR4.


bovine, corpus luteum, toll-like receptors.


Akira S. 2003. Toll-like receptor signaling. J Biol Chem, 278:38105-38108.

Amjadi F, Salehi E, Mehdizadeh M, Aflatoonian R. 2014. Role of the innate immunity in female reproductive tract. Adv Biomed Res, 3:1.

Arosh JA, Parent J, Chapdelaine P, Sirois J, Fortier MA. 2002. Expression of cyclooxygenases 1 and 2 and prostaglandin E synthase in bovine endometrial tissue during the estrous cycle. Biol Reprod, 67:161-169.

Atli MO, Mehta V, Baruah KK, Bender RW, Bastos MR, Guenther JN, Luo W, Vezina CM, Wiltbank MC. 2011. Induction and localization of five immediate early genes (IEGs) in the bovine corpus luteum (CL) at 30 min after prostaglandin F2 alpha (PGF) treatment. Reprod Dom Anim, 46:(supp1)87-87.

Atli MO, Bender RW, Mehta V, Bastos MR, Luo W, Vezina CM, Wiltbank MC. 2012. Patterns of gene expression in the bovine corpus luteum following repeated intrauterine infusions of low doses of prostaglandin F2alpha. Biol Reprod, 86:130.

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. Reprod Biol Endocrinol, 18:6:53.

Fitzgerald KA, Palsson-McDermott EM, Bowie AG, Jefferies CA, Mansell AS, Brady G, Brint E, Dunne A, Gray P, Harte MT, McMurray D, Smith DE, Sims JE, Bird TA, O'Neill LA. 2001. Mal (MyD88-adapterlike) is required for Toll-like receptor-4 signal transduction. Nature, 413:78-83.

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.

Horne AW, Stock SJ, King AE. 2008. Innate immunity and disorders of the female reproductive tract. Reproduction, 135:739-749.

Kannaki TR, Shanmugam M, Verma PC. 2011. Tolllike receptors and their role in animal reproduction. Anim Reprod Sci, 125:1-12.

Kaya MS, Kose M, Guzeloglu A, Kiyma Z, Atli MO. 2017. Early pregnancy-related changes in toll-like receptor expression in ovine trophoblasts and peripheral blood leukocytes. Theriogenology, 93:40-45.

Koga K, Mor G. 2008.Expression and function of tolllike receptors at the maternal-fetal interface. Reprod Sci, 15:231-242.

Liptak AR, Sullivan BT, Henkes LE, Wijayagunawardane MP, Miyamoto A, Davis JS, Rueda BR, Townson DH. 2005. Cooperative expression of monocyte chemoattractant protein 1 within the bovine corpus luteum: evidence of immune cell-endothelial cell interactions in a coculture system. Biol Reprod, 72:1169-1176.

Livak KJ, Schmittgen TD. 2001. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods, 25:402- 408.

Lüttgenau J, Herzog K, Strüve K, Latter S, Boos A, Bruckmaier RM, Bollwein H, Kowalewski MP. 2016. LPS-mediated effects and spatio-temporal expression of TLR2 and TLR4 in the bovine corpus luteum. Reproduction, 151:391-399.

Mamluk R, Chen D, Greber Y, Davis JS, Meidan R. 1998.Characterization of messenger ribonucleic acid expression for prostaglandin F2 alpha and luteinizing hormone receptors in various bovine luteal cell types. Biol Reprod, 58:849-856.

McGettrick AF, Brint EK, Palsson-McDermott EM, Rowe DC, Golenbock DT, Gay NJ, Fitzgerald KA, O'Neill LA. 2006. Trif-related adapter molecule is phosphorylated by PKC{epsilon} during Toll-like receptor 4 signaling. Proc Natl Acad Sci, 103:9196- 9201. Mondal M, Schilling B, Folger J, Steibel JP, Buchnick H, Zalman Y, Ireland JJ, Meidan R, Smith GW. 2011. Deciphering the luteal transcriptome: potential mechanisms mediating stage-specific luteolytic response of the corpus luteum to prostaglandin F(2)alpha. Physiol Genomics, 43:447- 456.

Pate JL, Johnson-Larson CJ, Ottobre JS. 2012. Life or death decisions in the corpus luteum. Reprod Domest Anim, 47:297-303.

Pate JL, Landis Keyes P. 2001. Immune cells in the corpus luteum: friends or foes? Reproduction, 122:665- 676.

Penny LA. 2000. Monocyte chemoattractant protein 1 in luteolysis. Rev Reprod, 5:63-66.

Piccinini AM, Midwood KS. 2010 DAMPening Inflammation by modulating TLR signaling. Mediators of Inflammation, Article ID 672395, doi:10.1155/2010/672395.

Poole DH, Pate JL. 2012. Luteal microenvironment directs resident T lymphocyte function in cows. Biol Reprod, 86:1-10.

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

Sen A, Wright M, Inskeep EK, Flores JA. 2006. Participation of specific PKC isozymes in the inhibitory effect of ET-1 on progesterone accumulation in cells isolated from early- and mid-phase corpora lutea. Domest Anim Endocrinol, 31:284-299.

Shirasuna K, Jiemtaweeboon S, Raddatz S, Nitta A, Schuberth HJ, Bollwein H, Shimizu T, Miyamoto A. 2012. Rapid accumulation of polymorphonuclear neutrophils in the corpus luteum during prostaglandin F(2alpha)-induced luteolysis in the cow. PloS ONE, 7: e29054.

Silva E, Leitao S, Henriques S, Kowalewski MP, Hoffmann B, Ferreira-Dias G, da Costa LL, Mateus L. 2010. Gene transcription of TLR2, TLR4, LPS ligands and prostaglandin synthesis enzymes are upregulated in canine uteri with cystic endometrial hyperplasia-pyometra complex. J Reprod Immunol, 84:66-74.

Skarzynski DJ, Okuda K. 2010. Inter- and intracellular mechanisms of prostaglandin F(2 alpha) action during corpus luteum regression in cattle. Soc Reprod Fertil, 67:305-324.

Wiltbank MC. 1994. Cell-types and hormonal mechanisms associated with mid-cycle corpus-luteum function. J Anim Sci, 72(7):1873-1883.

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