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Thyroid peroxidase in human endometrium and placenta: a potential target for anti-TPO antibodies

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Abstract

Autoimmune thyroid disease is the most common endocrine disorder during pregnancy. Thyroid autoantibodies (TAs) have been suggested to serve a role in implantation failure and spontaneous abortion. Until now, there are no data on the potential interaction of TAs with human reproductive organs. Here, we set out for the first time to test this hypothesis by studying the expression of thyroid peroxidase (TPO) at gene and protein level in human reproductive organs. Endometrial samples were taken from normal women, and placenta tissues were collected after full-term caesarian section. Expression of TPO messenger RNA (mRNA) was investigated by qRT-PCR. In addition, polyclonal anti-TPO antibodies were produced and the expression of TPO protein in mentioned tissues was evaluated by immunohistochemistry and Western blot analysis. The reactivity of anti-TPO antibody in human embryos was evaluated by immunofluorescent staining. For the first time, our study showed that TPO is expressed at gene and protein levels in endometrium and placenta. TPO expression was mainly localized to glandular and luminal epithelial cells in the endometrium. In placenta, the syncytiotrophoblasts and invasive trophoblast cells were the main cell types that expressed TPO protein. Specific band of approximately 110 kDa was observed in all endometrial and placental tissues by Western blot analysis. However, no expression of TPO protein was observed in human embryo. TPO expression in endometrium and placenta may explain higher frequency of abortion and infertility in patients with thyroid autoimmunity.

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References

  1. Wilcox AJ, Weinberg CR, O'Connor JF, et al. Incidence of early loss of pregnancy. N Engl J Med. 1988;319(4):189–94.

    Article  CAS  PubMed  Google Scholar 

  2. Healy DL, Trounson AO, Andersen AN. Female infertility: causes and treatment. Lancet. 1994;343(8912):1539–44.

    Article  CAS  PubMed  Google Scholar 

  3. Thonneau P, Marchand S, Tallec A, et al. Incidence and main causes of infertility in a resident population (1,850,000) of three French regions (1988–1989). Hum Reprod. 1991;6(6):811–6.

    Article  CAS  PubMed  Google Scholar 

  4. Shoenfeld Y, Carp HJ, Molina V, et al. Autoantibodies and prediction of reproductive failure. Am J Reprod Immunol. 2006;56(5–6):337–44.

    Article  CAS  PubMed  Google Scholar 

  5. Poppe K, Glinoer D. Thyroid autoimmunity and hypothyroidism before and during pregnancy. Hum Reprod Update. 2003;9(2):149–61.

    Article  PubMed  Google Scholar 

  6. Dallas JS. Autoimmune thyroid disease and pregnancy: relevance for the child. Autoimmunity. 2003;36(6–7):339–50.

    Article  PubMed  Google Scholar 

  7. Pedersen IB, Knudsen N, Jorgensen T, et al. Thyroid peroxidase and thyroglobulin autoantibodies in a large survey of populations with mild and moderate iodine deficiency. Clin Endocrinol (Oxf). 2003;58(1):36–42.

    Article  Google Scholar 

  8. Tunbridge WM, Evered DC, Hall R, et al. The spectrum of thyroid disease in a community: the Whickham survey. Clin Endocrinol (Oxf). 1977;7(6):481–93.

    Article  CAS  Google Scholar 

  9. de Escobar GM, Obregon MJ, del Rey FE. Maternal thyroid hormones early in pregnancy and fetal brain development. Best Pract Res Clin Endocrinol Metab. 2004;18(2):225–48.

    Article  PubMed  CAS  Google Scholar 

  10. Vitale L, Piovesan A, Antonaros F, et al. A molecular view of the normal human thyroid structure and function reconstructed from its reference transcriptome map. BMC Genom. 2017;18(1):739.

    Article  CAS  Google Scholar 

  11. Cianfarani F, Baldini E, Cavalli A, et al. TSH receptor and thyroid-specific gene expression in human skin. J Invest Dermatol. 2010;130(1):93–101.

    Article  CAS  PubMed  Google Scholar 

  12. Spitzweg C, Joba W, Heufelder AE. Expression of thyroid-related genes in human thymus. Thyroid. 1999;9(2):133–41.

    Article  CAS  PubMed  Google Scholar 

  13. Muller I, Giani C, Zhang L, et al. Does thyroid peroxidase provide an antigenic link between thyroid autoimmunity and breast cancer? Int J Cancer. 2014;134(7):1706–14.

    Article  CAS  PubMed  Google Scholar 

  14. Godlewska M, Arczewska KD, Rudzinska M, et al. Thyroid peroxidase (TPO) expressed in thyroid and breast tissues shows similar antigenic properties. PLoS ONE. 2017;12(6):e0179066.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  15. Godlewska M, Krasuska W, Czarnocka B. Biochemical properties of thyroid peroxidase (TPO) expressed in human breast and mammary-derived cell lines. PLoS ONE. 2018;13(3):e0193624.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  16. Godlewska M, Banga PJ. Thyroid peroxidase as a dual active site enzyme: focus on biosynthesis, hormonogenesis and thyroid disorders of autoimmunity and cancer. Biochimie. 2019;160:34–45.

    Article  CAS  PubMed  Google Scholar 

  17. Matalon ST, Blank M, Ornoy A, Shoenfeld Y. The association between anti-thyroid antibodies and pregnancy loss. Am J Reprod Immunol. 2001;45(2):72–7.

    Article  CAS  PubMed  Google Scholar 

  18. Marai I, Carp H, Shai S, et al. Autoantibody panel screening in recurrent miscarriages. Am J Reprod Immunol. 2004;51(3):235–40.

    Article  CAS  PubMed  Google Scholar 

  19. Stricker RB. Antithyroid antibodies in recurrent pregnancy loss. Am J Obstet Gynecol. 1994;170(3):956–7.

    Article  CAS  PubMed  Google Scholar 

  20. Bussen S, Steck T, Dietl J. Increased prevalence of thyroid antibodies in euthyroid women with a history of recurrent in-vitro fertilization failure. Hum Reprod. 2000;15(3):545–8.

    Article  CAS  PubMed  Google Scholar 

  21. Esplin MS, Branch DW, Silver R, Stagnaro-Green A. Thyroid autoantibodies are not associated with recurrent pregnancy loss. Am J Obstet Gynecol. 1998;179(6 Pt 1):1583–6.

    Article  CAS  PubMed  Google Scholar 

  22. Geva E, Lessing JB, Lerner-Geva L, et al. The presence of antithyroid antibodies in euthyroid patients with unexplained infertility and tubal obstruction. Am J Reprod Immunol. 1997;37(2):184–6.

    Article  CAS  PubMed  Google Scholar 

  23. Lejeune B, Grun JP, de Nayer P, Servais G, Glinoer D. Antithyroid antibodies underlying thyroid abnormalities and miscarriage or pregnancy induced hypertension. Br J Obstet Gynaecol. 1993;100(7):669–72.

    Article  CAS  PubMed  Google Scholar 

  24. Muller AF, Drexhage HA, Berghout A. Postpartum thyroiditis and autoimmune thyroiditis in women of childbearing age: recent insights and consequences for antenatal and postnatal care. Endocr Rev. 2001;22(5):605–30.

    Article  CAS  PubMed  Google Scholar 

  25. Montoro MN. Management of hypothyroidism during pregnancy. Clin Obstet Gynecol. 1997;40(1):65–80.

    Article  CAS  PubMed  Google Scholar 

  26. Lee YL, Ng HP, Lau KS, et al. Increased fetal abortion rate in autoimmune thyroid disease is related to circulating TPO autoantibodies in an autoimmune thyroiditis animal model. Fertil Steril. 2009;91(5 Suppl):2104–9.

    Article  PubMed  Google Scholar 

  27. Gora M, Gardas A, Wiktorowicz W, et al. Evaluation of conformational epitopes on thyroid peroxidase by antipeptide antibody binding and mutagenesis. Clin Exp Immunol. 2004;136(1):137–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Zarnani AH, Moazzeni SM, Shokri F, Salehnia M, Jeddi Tehrani M. Analysis of endometrial myeloid and lymphoid dendritic cells during mouse estrous cycle. J Reprod Immunol. 2006;71(1):28–40.

    Article  CAS  PubMed  Google Scholar 

  29. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2001;25(4):402–8.

    Article  CAS  PubMed  Google Scholar 

  30. Kaider AS, Kaider BD, Janowicz PB, Roussev RG. Immunodiagnostic evaluation in women with reproductive failure. Am J Reprod Immunol. 1999;42(6):335–46.

    Article  CAS  PubMed  Google Scholar 

  31. Tincani A, Rebaioli CB, Frassi M, et al. Pregnancy and autoimmunity: maternal treatment and maternal disease influence on pregnancy outcome. Autoimmun Rev. 2005;4(7):423–8.

    Article  CAS  PubMed  Google Scholar 

  32. Iijima T, Tada H, Hidaka Y, et al. Effects of autoantibodies on the course of pregnancy and fetal growth. Obstet Gynecol. 1997;90(3):364–9.

    Article  CAS  PubMed  Google Scholar 

  33. Pratt DE, Kaberlein G, Dudkiewicz A, Karande V, Gleicher N. The association of antithyroid antibodies in euthyroid nonpregnant women with recurrent first trimester abortions in the next pregnancy. Fertil Steril. 1993;60(6):1001–5.

    Article  CAS  PubMed  Google Scholar 

  34. Glinoer D, Soto MF, Bourdoux P, et al. Pregnancy in patients with mild thyroid abnormalities: maternal and neonatal repercussions. J Clin Endocrinol Metab. 1991;73(2):421–7.

    Article  CAS  PubMed  Google Scholar 

  35. Singh A, Dantas ZN, Stone SC, Asch RH. Presence of thyroid antibodies in early reproductive failure: biochemical versus clinical pregnancies. Fertil Steril. 1995;63(2):277–81.

    Article  CAS  PubMed  Google Scholar 

  36. Stagnaro-Green A, Roman SH, Cobin RH, et al. Detection of at-risk pregnancy by means of highly sensitive assays for thyroid autoantibodies. JAMA. 1990;264(11):1422–5.

    Article  CAS  PubMed  Google Scholar 

  37. Matalon ST, Blank M, Levy Y, et al. The pathogenic role of anti-thyroglobulin antibody on pregnancy: evidence from an active immunization model in mice. Hum Reprod. 2003;18(5):1094–9.

    Article  PubMed  CAS  Google Scholar 

  38. Moravej A, Jeddi-Tehrani M, Salek-Moghaddam AR, et al. Evaluation of thyroglobulin expression in murine reproductive organs during pregnancy. Am J Reprod Immunol. 2010;64(2):97–103.

    CAS  PubMed  Google Scholar 

  39. Stassi G, De Maria R. Autoimmune thyroid disease: new models of cell death in autoimmunity. Nat Rev Immunol. 2002;2(3):195–204.

    Article  CAS  PubMed  Google Scholar 

  40. Calder EA, Penhale WJ, McLeman D, Barnes EW, Irvine WJ. Lymphocyte-dependent antibody-mediated cytotoxicity in Hashimoto thyroiditis. Clin Exp Immunol. 1973;14(2):153–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Aghajanova L, Stavreus-Evers A, Lindeberg M, et al. Thyroid-stimulating hormone receptor and thyroid hormone receptors are involved in human endometrial physiology. Fertil Steril. 2011;95(1):230–7 (e1–2).

    Article  CAS  PubMed  Google Scholar 

  42. Fayadat L, Niccoli-Sire P, Lanet J, Franc JL. Human thyroperoxidase is largely retained and rapidly degraded in the endoplasmic reticulum Its N-glycans are required for folding and intracellular trafficking. Endocrinology. 1998;139(10):4277–85.

    Article  CAS  PubMed  Google Scholar 

  43. Lai OF, Zaiden N, Goh SS, et al. Detection of thyroid peroxidase mRNA and protein in orbital tissue. Eur J Endocrinol. 2006;155(2):213–8.

    Article  CAS  PubMed  Google Scholar 

  44. Farahati J, Roggenbuck D, Gilman E, et al. Anti-thyroid peroxidase antibodies are associated with the absence of distant metastases in patients with newly diagnosed breast cancer. Clin Chem Lab Med. 2012;50(4):709–14.

    Article  CAS  PubMed  Google Scholar 

  45. Smyth PP, Shering SG, Kilbane MT, et al. Serum thyroid peroxidase autoantibodies, thyroid volume, and outcome in breast carcinoma. J Clin Endocrinol Metab. 1998;83(8):2711–6.

    CAS  PubMed  Google Scholar 

  46. Fiore E, Giustarini E, Mammoli C, et al. Favorable predictive value of thyroid autoimmunity in high aggressive breast cancer. J Endocrinol Invest. 2007;30(9):734–8.

    Article  CAS  PubMed  Google Scholar 

  47. Muller I, Kilburn LS, Taylor PN, et al. TPOAb and Thyroid function are not associated with breast cancer outcome: evidence from a Large-Scale Study Using Data from the Taxotere as Adjuvant Chemotherapy Trial (TACT, CRUK01/001). Eur Thyroid J. 2017;6(4):197–207.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

The authors would like to thank all participants who entered our study.

Funding

This work was supported partially by grant of Isfahan University of Medical Sciences (research Grant No. 395057) and also by the grant from Iran National Science Foundation (research Grant No. 95818097), and Avicenna Research Institute (research Grant No. 96–035), Islamic Republic of Iran. The funding body was not involved in collection, analysis, interpretation of data, and in writing of the manuscript.

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Correspondence to Abbas Rezaei or Amir Hassan Zarnani.

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The authors declare that they have no conflict of interests concerning this article.

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All procedures performed in studies involving human participants were in accordance with the Ethics Committee of Isfahan University of Medical Sciences (Code of Ethics: IR.MUI.REC.1395.3.057) and ARI infertility clinic ethics committee (Code of Ethics: IR.ACECR.AVICENNA.REC.1397.025) and with the Helsinki declaration and its later amendments or comparable ethical standards.

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Rahnama, R., Mahmoudi, AR., Kazemnejad, S. et al. Thyroid peroxidase in human endometrium and placenta: a potential target for anti-TPO antibodies. Clin Exp Med 21, 79–88 (2021). https://doi.org/10.1007/s10238-020-00663-y

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  • DOI: https://doi.org/10.1007/s10238-020-00663-y

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