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Expressions of tumor necrosis factor-α, its receptor I, II and receptor-associated factor 2 in the porcine corpus luteum during the estrous cycle and early pregnancy

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Abstract

We examined the gene and protein levels of tumor necrosis factor (TNF)-α, its receptors (types I and II, designated TNF-RI and TNF-RII, respectively), TNF receptor-associated factor 2 (TRAF2) and morphological features in the porcine corpus luteum (CL), on Days 13 and 17 (Day 0 = the last day of estrus) of the estrous cycle or of early pregnancy. Gene expression levels of TNF-α, TNF-RI, TNF-RII and TRAF2 were unaffected by the day or reproductive status. TNF-α concentration was significantly higher in the CL on Day 17 of pregnancy than on Day 13 of pregnancy and on day 17 of the estrous cycle. The TNF-RI protein level was significantly higher in the CL on Days 13 and 17 of pregnancy than those of the estrous cycle, significantly increasing on Day 17 compared with those on Day 13 in pregnancy. In relation to TNF-RII protein levels, although there were no change during pregnancy, there was a tendency (P = 0.0524) to up-regulate as pregnancy proceeded. In estrous cycle, TNF-RII protein levels decreased significantly as luteolysis proceeded. TRAF2 protein level was significantly higher in the CL on Days 13 and 17 of pregnancy than during estrous. There were few apoptotic bodies in the CL between Days 13 and 17 of pregnancy than during esrous. There were few apoptotic bodies in the CL between Days 13 and 17 of pregnancy. The number of apoptotic bodies was much greater than the CL on Day 17 of the estrous than those of pregnancy. Thus, the TNF-α and TNF-RI and TNF-RII pathways including the TRAF2 protein, known to control of cell differentiation, tissue renewal and apoptosis, might participate in maintaining the porcine CL during early pregnancy.

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References

  • Adashi EY, Resnick CE, Packman JN, Hurwitz A, Payne DW (1990) Cytokine-mediated regulation of ovarian function: tumor necrosis factor alpha inhibits gonadotropin-supported progesterone accumulation by differentiating and luteinized murine granulosa cells. Am J Obstet Gynecol 162:889–899

    Article  CAS  PubMed  Google Scholar 

  • Appleby SB, Ristimaki A, Neilson K, Narko K, Hla T (1994) Structure of the human cyclo-oxygenase-2 gene. Biochem J 302:723–727

    CAS  PubMed  Google Scholar 

  • Arch RH, Gedrich RW, Thompson CB (1998) Tumor necrosis factor receptor-associated factors (TRAFs)—a family of adapter proteins that regulates life and death. Genes Dev 12:2821–2830

    Article  CAS  PubMed  Google Scholar 

  • Baeuerle PA, Henkel T (1994) Function and activation of NF-κB in the immune system. Annu Rev Immunol 12:141–179

    Article  CAS  PubMed  Google Scholar 

  • Baud V, Liu ZG, Bennett B, Suzuki N, Xia Y, Karin M (1999) Signaling by proinflammatory cytokines: oligomerization of TRAF2 and TRAF6 is sufficient for JNK and IKK activation and target gene induction via an amino-terminal effector domain. Genes Dev 13:1297–1308

    Article  CAS  PubMed  Google Scholar 

  • Benyo DF, Pate JL (1992) Tumor necrosis factor-alpha alters bovine luteal cell synthetic capacity and viability. Endocrinology 130:854–860

    CAS  PubMed  Google Scholar 

  • Beutler B, Cerami A (1989) The biology of cachectin/TNF—a primary mediator of the host response. Annu Rev Immunol 7:625–655

    Article  CAS  PubMed  Google Scholar 

  • Bornstein SR, Rutkowski H, Vrezas I (2004) Cytokine and steroidogenesis. Mol Cell Endocrinol 215:135–141

    Article  CAS  PubMed  Google Scholar 

  • Bumbasirevic V, Skaro-Milic A, Mircic A, Djuricic B (1995) Apoptosis induced by microtubule disrupting drugs in normal murine thymocytes in vitro. Scanning Microsc 9:509–518

    CAS  PubMed  Google Scholar 

  • Christiansen OB (1996) A fresh look at the causes and treatments of recurrent miscarriage, especially its immunological aspects. Hum Reprod Update 2:271–279

    Article  CAS  PubMed  Google Scholar 

  • Crombie PR (1972) The morphology and ultrastructure of the pig’s placenta throughout pregnancy. Ph.D. Dissertation, University of Cambridge, Cambridge, England

  • Cybulsky MI, Gimbrone MA (1991) Endothelial expression of a mononuclear leukocyte adhesion molecule during atherogenesis. Science 251:788–791

    Article  CAS  PubMed  Google Scholar 

  • Diaz FJ, Luo W, Wiltbank MC (2013) Prostaglandin F2α regulation of mRNA for activating protein 1 transcriptional factors in porcine corpora lutea (CL): lack of induction of JUN and JUND in CL without luteolytic capacity. Domest Anim Endocrinol 44:98–108

    Article  CAS  PubMed  Google Scholar 

  • Friedman A, Weiss S, Levy N, Meidan R (2000) Role of tumor necrosis factor alpha and its type I receptor in luteal regression: induction of programmed cell death in bovine corpus luteum-derived endothelial cells. Biol Reprod 63:1905–1912

    Article  CAS  PubMed  Google Scholar 

  • Gesslein B, Håkansson G, Gustafsson L, Ekström P, Malmsjö M (2010) Tumor necrosis factor and its receptors in the neuroretina and retinal vasculature after ischemia-reperfusion injury in the pig retina. Mol Vis 16:2317–2327

    CAS  PubMed  Google Scholar 

  • Haider S, Knöfler M (2009) Human tumor necrosis factor: physiological and pathological roles in placenta and endometrium. Placenta 30:111–123

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • He J, Bazan HE (2006) Synergistic effect of platelet-activating factor and tumor necrosis factor-α on corneal myofibroblast apoptosis. Invest ophthalmol Vis Sci 47:883–891

    Article  PubMed  Google Scholar 

  • Hehnke-Vagnoni KE, Clark CL, Taylor MJ, Ford SP (1995) Presence and localization of tumor necrosis factor α in the corpus luteum of nonpregnant and pregnant pigs. Biol Reprod 53:1339–1344

    Article  CAS  PubMed  Google Scholar 

  • Jabbour HN, Boddy SC (2003) Prostaglandin E2 induces proliferation of glandular epithelial cells of the human endometrium via extracellular regulated kinase 1/2-mediated pathway. J Clin Endocrinol Metab 88:4481–4487

    Article  CAS  PubMed  Google Scholar 

  • Klentzeris LD, Bulmer JN, Warren MA, Morrison L, Li TC, Cooke ID (1994) Lymphoid tissue in the endometrium of woman with unexplained infertility: morphometric and immunohistochemical aspects. Hum Reprod 9:646–652

    CAS  PubMed  Google Scholar 

  • Knapczyk K, Duda M, Durlej M, Galas J, Koziorowski M, Slomczynska M (2008) Expression of estrogen receptor α (ERα) and estrogen receptor β (ERβ) in the ovarian follicles and corpora lutea of pregnant swine. Domest Anim Endocrinol 35:170–179

    Article  CAS  PubMed  Google Scholar 

  • Korzekwa A, Murakami S, Woclawek-Potocka I, Bah MM, Okuda K, Skarzynski DJ (2008) The influence of tumor necrosis factor α (TNF) on the secretory function of bovine corpus luteum: TNF and its receptors expression during the estrous cycle. Reprod Biol 8:245–262

    Article  PubMed  Google Scholar 

  • Manabe N, Matsuda-Minehata F, Goto Y, Maeda A, Cheng Y, Nakagawa S, Inoue N, Wongpanit K, Jin H, Gonda H, Li J (2008) Role of cell death ligand and receptor system on regulation of follicular atresia in pig ovaries. Reprod Domest Anim 43:268–272

    Article  PubMed  Google Scholar 

  • Miyamoto Y, Sakumoto R, Sakabe Y, Miyake M, Okano A, Okuda K (2002) Tumor necrosis factor-alpha receptors are present in the corpus luteum throughout the oestrous cycle and during the early gestation period in pigs. Reprod Domest Anim 37:105–110

    Article  CAS  PubMed  Google Scholar 

  • Nakayama M, Manabe N, Inoue N, Matsui T, Miyamoto H (2003) Changes in the expression of tumor necrosis factor (TNF)-α, TNF-α receptor (TNFR) 2, and TNFR-associated factor 2 in granulosa cells during atresia in pig ovaries. Biol Reprod 68:530–535

    Article  CAS  PubMed  Google Scholar 

  • Natoli G, Costanzo A, Guido F, Moretti F, Levrero M (1998) Apoptotic, non-apoptotic, and anti-apoptotic pathways of tumor necrosis factor signaling. Biochem Pharmacol 56:915–920

    Article  CAS  PubMed  Google Scholar 

  • Niswender GD, Juengel JL, Silva PJ, Rollyson MK, Mcintush EW (2000) Mechanisms controlling the function and life span of the corpus luteum. Physiol Rev 80:1–29

    CAS  PubMed  Google Scholar 

  • Okuda K, Sakumoto R (2003) Multiple roles of TNF super family members in corpus luteum function. Reprod Biol Endocrinol 1:95

    Article  PubMed Central  PubMed  Google Scholar 

  • Parker VJ, Douglas AJ (2010) Stress in early pregnancy: maternal neuro-endocrine-immune responses and effects. J Reprod Immunol 85:86–92

    Article  CAS  PubMed  Google Scholar 

  • Peluffo MC, Young KA, Hennebold JD, Stouffer RL (2009) Expression and regulation of tumor necrosis factor (TNF) and TNF-receptor family members in the macaque corpus luteum during the menstrual cycle. Mol Reprod Dev 76:367–378

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Perry JS (1981) The mammalian fetal membranes. J Reprod Fertil 62:321–335

    Article  CAS  PubMed  Google Scholar 

  • Pitzel L, Jarry H, Wuttke W (1993) Effects and interactions of prostaglandin F2 alpha, oxytocin and cytokines on steroidogenesis of porcine luteal cells. Endocrinology 132:751–756

    CAS  PubMed  Google Scholar 

  • Prange-kiel J, Kreutzkamm C, Wehrenberg U, Rune GM (2001) Role of tumor necrosis factor in preovulatory follicles of swine. Biol Reprod 65:928–935

    Article  CAS  PubMed  Google Scholar 

  • Pru JK, Lynch MP, Davis JS, Rueda BR (2003) Signaling mechanisms in tumor necrosis factor α-induced death of microvascular endothelial cells of the corpus luteum. Reprod Biol Endocrinol 1:17

    Article  PubMed Central  PubMed  Google Scholar 

  • Reynolds LP, Killilea SD, Redmer DA (1992) Angiogenesis in the female reproductive system. FASEB J 6:886–892

    CAS  PubMed  Google Scholar 

  • Reynolds LP, Grazul-Bilska AT, Killilea SD, Redmer DA (1994) Mitogenic factors of corpora lutea. Prog Growth Factor Res 5:159–175

    Article  CAS  PubMed  Google Scholar 

  • Richards RG, Almond GW (1994) Identification and distribution of tumor necrosis factor alpha receptors in pig corpora lutea. Biol Reprod 51:1285–1291

    Article  CAS  PubMed  Google Scholar 

  • Richardson MC (1986) Hormonal control of ovarian luteal cells. Oxf Rev Reprod Biol 8:321–378

    CAS  PubMed  Google Scholar 

  • Rosengren S, Firestein GS, Boyle DL (2003) Measurement of inflammatory biomarkers in synovial tissue extracts by enzyme-linked immunosorbent assay. Clin Diagn Lab Immunol 10:1002–1010

    CAS  PubMed Central  PubMed  Google Scholar 

  • Rothe M, Sarma V, Dixit VM, Goeddel DV (1995) TRAF2-mediated activation of NF-κB by TNF receptor 2 and CD40. Science 269:5229

    Article  Google Scholar 

  • Sakumoto R, Berisha B, Kawate N, Schams D, Okuda K (2000a) Tumor necrosis factor-alpha and its receptor in bovine corpus luteum throughout the estrous cycle. Biol Reprod 62:192–199

    Article  CAS  PubMed  Google Scholar 

  • Sakumoto R, Murakami S, Kishi H, Iga K, Okano A, Okuda K (2000b) Tumor necrosis factor-alpha and its receptor in the corpus luteum of pregnant cows. Mol Reprod Dev 55:406–411

    Article  CAS  PubMed  Google Scholar 

  • Sakumoto R, Vermehren M, Kenngott RA, Okuda K, Sinowatz F (2011) Localization of gene and protein expressions of tumor necrosis factor-α (TNF), and TNF receptor types I and II in the bovine corpus luteum during the estrous cycle. J Anim Sci 89:3040–3047

    Article  CAS  PubMed  Google Scholar 

  • SAS (2008) SAS User’s Guide: Statistics (version 9.2). Cary, NC: Statistical Analysis System Institute Inc.

  • Shu HB, Takeuchi M, Goeddel DV (1996) The tumor necrosis factor receptor 2 signal transducers TRAF2 and c-IAP1 are components of the tumor necrosis factor receptor 1 signaling complex. Proc Natl Acad Sci USA 93:13973–13978

    Article  CAS  PubMed  Google Scholar 

  • Smolinska N, Kaminski T, Siawrys G, Przala J (2007) Long form of leptin receptor gene and protein expression in the porcine ovary during the estrous cycle and early pregnancy. Reprod Biol 7:17–39

    PubMed  Google Scholar 

  • Stray-Pedersen B, Stray-Pedersen M (1984) Etiologic factors and subsequent reproductive performance in 195 couples with a prior history of habitual abortion. Am J Obstet Gynecol 148:140–146

    Article  CAS  PubMed  Google Scholar 

  • Sugino N, Suzuki T, Kashida S, Karube A, Takiguchi S, Kato H (2000) Expression of Bcl-2 and Bax in the human corpus luteum during the menstrual cycle and in early pregnancy: regulation by human chorionic gonadotropin. J Clin Endocrinol Metab 85:4379–4386

    CAS  PubMed  Google Scholar 

  • Terranova PF (1997) Potential roles of tumor necrosis factor-α in follicular development, ovulation, and the life span of the corpus luteum. Domest Anim Endocrinol 14:1–15

    Article  CAS  PubMed  Google Scholar 

  • Waclawik A, Kaczmarek MM, Kowalczyk AE, Bogacki M, Ziecik AJ (2008) Expression of prostaglandin synthesis pathway enzymes in the porcine corpus luteum during the oestrous cycle and early pregnancy. Theriogenology 70:145–152

    Article  CAS  PubMed  Google Scholar 

  • Walczak H (2011) TNF and ubiquitin at the crossroads of gene activation, cell death, inflammation, and cancer. Immunol Rev 244:9–28

    Article  CAS  PubMed  Google Scholar 

  • Wallach D, Varfolomeev EE, Malinin NL, Goltsev YV, Kovalenko AV, Boldin MP (1999) Tumor necrosis factor receptor and Fas signaling mechanisms. Annu Rev Immunol 17:331–367

    Article  CAS  PubMed  Google Scholar 

  • Wasser SK (1999) Stress and reproductive failure: an evolutionary approach with applications to premature labor. Am J Obstet Gynecol 180:272–274

    Article  Google Scholar 

  • Wuttke W, Pitzel L, Knoke I, Theiling K, Jarry H (1997) Immune-endocrine interactions affecting luteal function in pigs. J Reprod Fertil Suppl 52:19–29

    CAS  PubMed  Google Scholar 

  • Wuttke W, Spiess S, Knoke I, Pitzel L, Leonhardt S, Jarry H (1998) Synergistic effects of prostaglandin F2α and tumor necrosis factor to induce luteolysis in the pig. Biol Reprod 58:1310–1315

    Article  CAS  PubMed  Google Scholar 

  • Zhao Y, Burbach JA, Roby KF, Terranova PF, Brannian JD (1998) Macrophages are the major source of tumor necrosis factor-α in the porcine corpus luteum. Biol Reprod 59:1385–1391

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Pathology and Pathophysiology Research Division, National Institute of Animal Health, Ibaraki, 305-0856, Japan

    Chie Suzuki, Koji Yoshioka, Manabu Yamada & Toru Miyamoto

  2. Animal Resource Science Center, The University of Tokyo, Ibaraki, 319-0206, Japan

    Noboru Manabe

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  1. Chie Suzuki
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  2. Koji Yoshioka
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  3. Manabu Yamada
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  4. Toru Miyamoto
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  5. Noboru Manabe
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Correspondence to Chie Suzuki.

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Suzuki, C., Yoshioka, K., Yamada, M. et al. Expressions of tumor necrosis factor-α, its receptor I, II and receptor-associated factor 2 in the porcine corpus luteum during the estrous cycle and early pregnancy. Vet Res Commun 38, 1–10 (2014). https://doi.org/10.1007/s11259-013-9575-9

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