Skip to main content

Advertisement

SpringerLink
Log in

The Effects of Anti-TGF-β1 on Epithelial–Mesenchymal Transition in the Pathogenesis of Adenomyosis

  • Original Article
  • Published:
Reproductive Sciences Aims and scope Submit manuscript

Abstract

Adenomyosis is defined as the presence of endometrial glands and stroma in the myometrium. The mechanisms associated with the pathogenesis of adenomyosis remain unclear. Epithelial–mesenchymal transition (EMT) is characterized by losing cell polarity and cell–cell adhesion together with gaining migratory and invasive properties of stromal cells to become mesenchymal stem cells. Transforming growth factor-β1 (TGF-β1), an anti-inflammatory cytokine secreted by multiple cell types, plays a crucial role in embryogenesis and tissue homeostasis. The induction of EMT and ultimate fibrosis by TGF-β1 is suggested to play a critical role in the pathogenesis of adenomyosis. Thus, this study aims to demonstrate the occurrence of EMT in and the effects of anti-TGF-β1 on the pathogenesis of adenomyosis. ICR mice were fed with 1 μg/g body weight of tamoxifen (TAM) by in the first 4 postnatal days (PNDs). Subsequently, the right and left uterine horns were correspondingly injected with or without 10 μg of anti-TGF-β1 neutralizing antibody on PND42 followed by sacrifice on PND64. E-cadherin, vimentin, and α-smooth muscle actin (α-SMA) expression in the uteri was evaluated by qRT-PCR, Western blot, and immunohistochemistry. Clusters of endometrial glands and increased numbers of vimentin-positive stromal cells in the disrupted α-SMA-positive myometrium were observed in the uteri from TAM-treated mice. Numbers of stromal cells in the myometrium and the disrupted myometrial continuity were reduced by anti-TGF-β1. Moreover, uterine expression of E-cadherin and vimentin/α-SMA was increased and decreased by anti-TGF-β1 treatment, respectively. Anti-TGF-β1 successfully inhibits EMT and the development of adenomyosis in mouse uteri.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Farquhar C, Brosens I. Medical and surgical management of adenomyosis. Best Pract Res Clin Obstet Gynaecol. 2006;20(4):603–16. https://doi.org/10.1016/j.bpobgyn.2006.01.012.

    Article  PubMed  Google Scholar 

  2. Lazzeri L, Di Giovanni A, Exacoustos C, Tosti C, Pinzauti S, Malzoni M, et al. Preoperative and postoperative clinical and Transvaginal ultrasound findings of adenomyosis in patients with deep infiltrating endometriosis. Reprod Sci. 2014;21(8):1027–33. https://doi.org/10.1177/1933719114522520.

    Article  PubMed  Google Scholar 

  3. Li X, Liu X, Guo SW. Clinical profiles of 710 premenopausal women with adenomyosis who underwent hysterectomy. J Obstet Gynaecol Res. 2014;40(2):485–94. https://doi.org/10.1111/jog.12211.

    Article  PubMed  Google Scholar 

  4. Vannuccini S, Luisi S, Tosti C, Sorbi F, Petraglia F. Role of medical therapy in the management of uterine adenomyosis. Fertil Steril. 2018;109(3):398–405. https://doi.org/10.1016/j.fertnstert.2018.01.013.

    Article  PubMed  Google Scholar 

  5. Bergeron C, Amant F, Ferenczy A. Pathology and physiopathology of adenomyosis. Best Pract Res Clin Obstet Gynaecol. 2006;20(4):511–21. https://doi.org/10.1016/j.bpobgyn.2006.01.016.

    Article  PubMed  Google Scholar 

  6. Parrott E, Butterworth M, Green A, White IN, Greaves P. Adenomyosis--a result of disordered stromal differentiation. Am J Pathol. 2001;159(2):623–30. https://doi.org/10.1016/S0002-9440(10)61733-6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Benagiano G, Habiba M, Brosens I. The pathophysiology of uterine adenomyosis: an update. Fertil Steril. 2012;98(3):572–9. https://doi.org/10.1016/j.fertnstert.2012.06.044.

    Article  CAS  PubMed  Google Scholar 

  8. Leyendecker G, Bilgicyildirim A, Inacker M, Stalf T, Huppert P, Mall G, et al. Adenomyosis and endometriosis. Re-visiting their association and further insights into the mechanisms of auto-traumatisation. An MRI study. Arch Gynecol Obstet. 2015;291(4):917–32. https://doi.org/10.1007/s00404-014-3437-8.

    Article  CAS  PubMed  Google Scholar 

  9. Shaked S, Jaffa AJ, Grisaru D, Elad D. Uterine peristalsis-induced stresses within the uterine wall may sprout adenomyosis. Biomech Model Mechanobiol. 2015;14(3):437–44. https://doi.org/10.1007/s10237-014-0614-4.

    Article  PubMed  Google Scholar 

  10. Hufnagel D, Li F, Cosar E, Krikun G, Taylor HS. The role of stem cells in the etiology and pathophysiology of endometriosis. Semin Reprod Med. 2015;33(5):333–40. https://doi.org/10.1055/s-0035-1564609.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Moll R, Levy R, Czernobilsky B, Hohlweg-Majert P, Dallenbach-Hellweg G, Franke WW. Cytokeratins of normal epithelia and some neoplasms of the female genital tract. Lab Investig. 1983;49(5):599–610.

    CAS  PubMed  Google Scholar 

  12. Gargett CE. Uterine stem cells: what is the evidence? Hum Reprod Update. 2007;13(1):87–101. https://doi.org/10.1093/humupd/dml045.

    Article  CAS  PubMed  Google Scholar 

  13. Gargett CE, Schwab KE, Deane JA. Endometrial stem/progenitor cells: the first 10 years. Hum Reprod Update. 2016;22(2):137–63. https://doi.org/10.1093/humupd/dmv051.

    Article  CAS  PubMed  Google Scholar 

  14. Vannuccini S, Tosti C, Carmona F, Huang SJ, Chapron C, Guo SW, et al. Pathogenesis of adenomyosis: an update on molecular mechanisms. Reprod BioMed Online. 2017;35(5):592–601. https://doi.org/10.1016/j.rbmo.2017.06.016.

    Article  CAS  PubMed  Google Scholar 

  15. Carrarelli P, Yen CF, Arcuri F, Funghi L, Tosti C, Wang TH, et al. Myostatin, follistatin and activin type II receptors are highly expressed in adenomyosis. Fertil Steril. 2015;104(3):744–52 e1. https://doi.org/10.1016/j.fertnstert.2015.05.032.

    Article  CAS  PubMed  Google Scholar 

  16. Streuli I, Santulli P, Chouzenoux S, Chapron C, Batteux F. Activation of the MAPK/ERK cell-signaling pathway in uterine smooth muscle cells of women with adenomyosis. Reprod Sci. 2015;22(12):1549–60. https://doi.org/10.1177/1933719115589410.

    Article  CAS  PubMed  Google Scholar 

  17. Chen YJ, Li HY, Huang CH, Twu NF, Yen MS, Wang PH, et al. Oestrogen-induced epithelial-mesenchymal transition of endometrial epithelial cells contributes to the development of adenomyosis. J Pathol. 2010;222(3):261–70. https://doi.org/10.1002/path.2761.

    Article  CAS  PubMed  Google Scholar 

  18. Oh SJ, Shin JH, Kim TH, Lee HS, Yoo JY, Ahn JY, et al. beta-Catenin activation contributes to the pathogenesis of adenomyosis through epithelial-mesenchymal transition. J Pathol. 2013;231(2):210–22. https://doi.org/10.1002/path.4224.

    Article  CAS  PubMed  Google Scholar 

  19. Polyak K, Weinberg RA. Transitions between epithelial and mesenchymal states: acquisition of malignant and stem cell traits. Nat Rev Cancer. 2009;9(4):265–73. https://doi.org/10.1038/nrc2620.

    Article  CAS  PubMed  Google Scholar 

  20. Zhang Q, Duan J, Liu X, Guo SW. Platelets drive smooth muscle metaplasia and fibrogenesis in endometriosis through epithelial-mesenchymal transition and fibroblast-to-myofibroblast transdifferentiation. Mol Cell Endocrinol. 2016;428:1–16. https://doi.org/10.1016/j.mce.2016.03.015.

    Article  CAS  PubMed  Google Scholar 

  21. Shen M, Liu X, Zhang H, Guo SW. Transforming growth factor beta1 signaling coincides with epithelial-mesenchymal transition and fibroblast-to-myofibroblast transdifferentiation in the development of adenomyosis in mice. Hum Reprod. 2016;31(2):355–69. https://doi.org/10.1093/humrep/dev314.

    Article  CAS  PubMed  Google Scholar 

  22. Liu X, Shen M, Qi Q, Zhang H, Guo SW. Corroborating evidence for platelet-induced epithelial-mesenchymal transition and fibroblast-to-myofibroblast transdifferentiation in the development of adenomyosis. Hum Reprod. 2016;31(4):734–49. https://doi.org/10.1093/humrep/dew018.

    Article  CAS  PubMed  Google Scholar 

  23. Zhu B, Chen Y, Shen X, Liu X, Guo SW. Anti-platelet therapy holds promises in treating adenomyosis: experimental evidence. Reprod Biol Endocrinol. 2016;14(1):66. https://doi.org/10.1186/s12958-016-0198-1.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Zhang X, Zhang P, Shao M, Zang X, Zhang J, Mao F, et al. SALL4 activates TGF-beta/SMAD signaling pathway to induce EMT and promote gastric cancer metastasis. Cancer Manag Res. 2018;10:4459–70. https://doi.org/10.2147/CMAR.S177373.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Ling J, Cai Z, Jin W, Zhuang X, Kan L, Wang F, et al. Silencing of c-Ski augments TGF-b1-induced epithelial-mesenchymal transition in cardiomyocyte H9C2 cells. Cardiol J. 2019;26(1):66–76. https://doi.org/10.5603/CJ.a2018.0009.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Ungefroren H, Sebens S, Groth S, Gieseler F, Fandrich F. The Src family kinase inhibitors PP2 and PP1 block TGF-beta1-mediated cellular responses by direct and differential inhibition of type I and type II TGF-beta receptors. Curr Cancer Drug Targets. 2011;11(4):524–35.

    Article  CAS  PubMed  Google Scholar 

  27. Alipio ZA, Jones N, Liao W, Yang J, Kulkarni S, Sree Kumar K, et al. Epithelial to mesenchymal transition (EMT) induced by bleomycin or TFG(b1)/EGF in murine induced pluripotent stem cell-derived alveolar type II-like cells. Differentiation. 2011;82(2):89–98. https://doi.org/10.1016/j.diff.2011.05.001.

    Article  CAS  PubMed  Google Scholar 

  28. Pardali E, Sanchez-Duffhues G, Gomez-Puerto MC, Ten Dijke P. TGF-beta-induced endothelial-mesenchymal transition in fibrotic diseases. Int J Mol Sci. 2017;18(10). https://doi.org/10.3390/ijms18102157.

  29. Johnson MC, Torres M, Alves A, Bacallao K, Fuentes A, Vega M, et al. Augmented cell survival in eutopic endometrium from women with endometriosis: expression of c-myc, TGF-beta1 and bax genes. Reprod Biol Endocrinol. 2005;3:45. https://doi.org/10.1186/1477-7827-3-45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Young VJ, Ahmad SF, Duncan WC, Horne AW. The role of TGF-beta in the pathophysiology of peritoneal endometriosis. Hum Reprod Update. 2017;23(5):548–59. https://doi.org/10.1093/humupd/dmx016.

    Article  CAS  PubMed  Google Scholar 

  31. Inagaki N, Ung L, Otani T, Wilkinson D, Lopata A. Uterine cavity matrix metalloproteinases and cytokines in patients with leiomyoma, adenomyosis or endometrial polyp. Eur J Obstet Gynecol Reprod Biol. 2003;111(2):197–203.

    Article  CAS  PubMed  Google Scholar 

  32. Struble J, Reid S, Bedaiwy MA. Adenomyosis: a clinical review of a challenging gynecologic condition. J Minim Invasive Gynecol. 2016;23(2):164–85. https://doi.org/10.1016/j.jmig.2015.09.018.

    Article  PubMed  Google Scholar 

  33. Stone RC, Pastar I, Ojeh N, Chen V, Liu S, Garzon KI, et al. Epithelial-mesenchymal transition in tissue repair and fibrosis. Cell Tissue Res. 2016;365(3):495–506. https://doi.org/10.1007/s00441-016-2464-0.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Dai C, Yang J, Liu Y. Transforming growth factor-beta1 potentiates renal tubular epithelial cell death by a mechanism independent of Smad signaling. J Biol Chem. 2003;278(14):12537–45. https://doi.org/10.1074/jbc.M300777200.

    Article  CAS  PubMed  Google Scholar 

  35. Dudas PL, Argentieri RL, Farrell FX. BMP-7 fails to attenuate TGF-beta1-induced epithelial-to-mesenchymal transition in human proximal tubule epithelial cells. Nephrol Dial Transplant. 2009;24(5):1406–16. https://doi.org/10.1093/ndt/gfn662.

    Article  CAS  PubMed  Google Scholar 

  36. Hu S, Yu W, Lv TJ, Chang CS, Li X, Jin J. Evidence of TGF-beta1 mediated epithelial-mesenchymal transition in immortalized benign prostatic hyperplasia cells. Mol Membr Biol. 2014;31(2–3):103–10. https://doi.org/10.3109/09687688.2014.894211.

    Article  CAS  PubMed  Google Scholar 

  37. Zhan M, Kanwar YS. Hierarchy of molecules in TGF-beta1 signaling relevant to myofibroblast activation and renal fibrosis. Am J Physiol Renal Physiol. 2014;307(4):F385–7. https://doi.org/10.1152/ajprenal.00338.2014.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Lovisa S, LeBleu VS, Tampe B, Sugimoto H, Vadnagara K, Carstens JL, et al. Epithelial-to-mesenchymal transition induces cell cycle arrest and parenchymal damage in renal fibrosis. Nat Med. 2015;21(9):998–1009. https://doi.org/10.1038/nm.3902.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Yanagita M. Inhibitors/antagonists of TGF-beta system in kidney fibrosis. Nephrol Dial Transplant. 2012;27(10):3686–91. https://doi.org/10.1093/ndt/gfs381.

    Article  CAS  PubMed  Google Scholar 

  40. Ji Y, Dou YN, Zhao QW, Zhang JZ, Yang Y, Wang T, et al. Paeoniflorin suppresses TGF-beta mediated epithelial-mesenchymal transition in pulmonary fibrosis through a Smad-dependent pathway. Acta Pharmacol Sin. 2016;37(6):794–804. https://doi.org/10.1038/aps.2016.36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Feng H, Lu JJ, Wang Y, Pei L, Chen X. Osthole inhibited TGF beta-induced epithelial-mesenchymal transition (EMT) by suppressing NF-kappaB mediated Snail activation in lung cancer A549 cells. Cell Adhes Migr. 2017;11(5–6):464–75. https://doi.org/10.1080/19336918.2016.1259058.

    Article  CAS  Google Scholar 

  42. McGaraughty S, Davis-Taber RA, Zhu CZ, Cole TB, Nikkel AL, Chhaya M, et al. Targeting anti-TGF-beta therapy to fibrotic kidneys with a dual specificity antibody approach. J Am Soc Nephrol. 2017;28(12):3616–26. https://doi.org/10.1681/ASN.2017010013.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Voelker J, Berg PH, Sheetz M, Duffin K, Shen T, Moser B, et al. Anti-TGF-beta1 antibody therapy in patients with diabetic nephropathy. J Am Soc Nephrol. 2017;28(3):953–62. https://doi.org/10.1681/ASN.2015111230.

    Article  CAS  PubMed  Google Scholar 

  44. Isaka Y. Targeting TGF-beta signaling in kidney fibrosis. Int J Mol Sci. 2018;19(9). https://doi.org/10.3390/ijms19092532.

  45. Green AR, Styles JA, Parrott EL, Gray D, Edwards RE, Smith AG, et al. Neonatal tamoxifen treatment of mice leads to adenomyosis but not uterine cancer. Exp Toxicol Pathol. 2005;56(4–5):255–63. https://doi.org/10.1016/j.etp.2004.10.001.

    Article  CAS  PubMed  Google Scholar 

  46. Kalluri R, Weinberg RA. The basics of epithelial-mesenchymal transition. J Clin Invest. 2009;119(6):1420–8. https://doi.org/10.1172/JCI39104.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Bird CC, McElin TW, Manalo-Estrella P. The elusive adenomyosis of the uterus--revisited. Am J Obstet Gynecol. 1972;112(5):583–93.

    Article  CAS  PubMed  Google Scholar 

  48. Skaland I, Janssen EA, Gudlaugsson E, Klos J, Kjellevold KH, Soiland H, et al. Phosphohistone H3 expression has much stronger prognostic value than classical prognosticators in invasive lymph node-negative breast cancer patients less than 55 years of age. Mod Pathol. 2007;20(12):1307–15. https://doi.org/10.1038/modpathol.3800972.

    Article  CAS  PubMed  Google Scholar 

  49. Kobayashi H, Kishi Y, Matsubara S. Mechanisms underlying adenomyosis-related Fibrogenesis. Gynecol Obstet Investig. 2019:1–12. https://doi.org/10.1159/000502822.

  50. Akamatsu T, Arai Y, Kosugi I, Kawasaki H, Meguro S, Sakao M, et al. Direct isolation of myofibroblasts and fibroblasts from bleomycin-injured lungs reveals their functional similarities and differences. Fibrogenesis Tissue Repair. 2013;6(1):15. https://doi.org/10.1186/1755-1536-6-15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Burns WC, Twigg SM, Forbes JM, Pete J, Tikellis C, Thallas-Bonke V, et al. Connective tissue growth factor plays an important role in advanced glycation end product-induced tubular epithelial-to-mesenchymal transition: implications for diabetic renal disease. J Am Soc Nephrol. 2006;17(9):2484–94. https://doi.org/10.1681/ASN.2006050525.

    Article  CAS  PubMed  Google Scholar 

  52. Qi S, Zhao X, Li M, Zhang X, Lu Z, Yang C, et al. Aberrant expression of Notch1/numb/snail signaling, an epithelial mesenchymal transition related pathway, in adenomyosis. Reprod Biol Endocrinol. 2015;13:96. https://doi.org/10.1186/s12958-015-0084-2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Jeong JH, Jang HJ, Kwak S, Sung GJ, Park SH, Song JH, et al. Novel TGF-beta1 inhibitor antagonizes TGF-beta1-induced epithelial-mesenchymal transition in human A549 lung cancer cells. J Cell Biochem. 2019;120(1):977–87. https://doi.org/10.1002/jcb.27460.

    Article  CAS  PubMed  Google Scholar 

  54. Nikitorowicz-Buniak J, Denton CP, Abraham D, Stratton R. Partially evoked epithelial-mesenchymal transition (EMT) is associated with increased TGFbeta signaling within lesional scleroderma skin. PLoS One. 2015;10(7):e0134092. https://doi.org/10.1371/journal.pone.0134092.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Guo S, Li Z, Yan L, Sun Y, Feng Y. GnRH agonist improves pregnancy outcome in mice with induced adenomyosis by restoring endometrial receptivity. Drug Des Devel Ther. 2018;12:1621–31. https://doi.org/10.2147/DDDT.S162541.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Lucarini L, Durante M, Lanzi C, Pini A, Boccalini G, Calosi L, et al. HYDAMTIQ, a selective PARP-1 inhibitor, improves bleomycin-induced lung fibrosis by dampening the TGF-beta/SMAD signalling pathway. J Cell Mol Med. 2017;21(2):324–35. https://doi.org/10.1111/jcmm.12967.

    Article  CAS  PubMed  Google Scholar 

  57. Feng T, Wei S, Wang Y, Fu X, Shi L, Qu L, et al. Rhein ameliorates adenomyosis by inhibiting NF-kappaB and beta-Catenin signaling pathway. Biomed Pharmacother. 2017;94:231–7. https://doi.org/10.1016/j.biopha.2017.07.089.

    Article  CAS  PubMed  Google Scholar 

  58. Chen Y, Zhu B, Zhang H, Liu X, Guo SW. Epigallocatechin-3-gallate reduces myometrial infiltration, uterine hyperactivity, and stress levels and alleviates generalized hyperalgesia in mice induced with adenomyosis. Reprod Sci. 2013;20(12):1478–91. https://doi.org/10.1177/1933719113488455.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Rice LM, Padilla CM, McLaughlin SR, Mathes A, Ziemek J, Goummih S, et al. Fresolimumab treatment decreases biomarkers and improves clinical symptoms in systemic sclerosis patients. J Clin Invest. 2015;125(7):2795–807. https://doi.org/10.1172/JCI77958.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Funding

This study was funded by E-Da hospital grants (EDAHP 106053 (NK), EDAHP107035 (NK), EDAHP108014 (NK), and EDAHP107015 (SJH).

Author information

Authors and Affiliations

  1. Department of Obstetrics and Gynecology, E-Da Hospital, Kaohsiung, Taiwan

    Nari Kay, Yu Chang & S. Joseph Huang

  2. Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, 100, Tzyou 1st Rd., Kaohsiung, 807, Taiwan

    Nari Kay, Jau-Ling Suen & Eing-Mei Tsai

  3. Department of Medical Research, E-Da Hospital, Kaohsiung, Taiwan

    Chun-Yen Huang, Li-Yen Shiu & Ya-Chun Yu

  4. School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan

    Yu Chang & S. Joseph Huang

  5. Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan

    Jau-Ling Suen

  6. Department of Obstetrics and Gynecology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan

    Eing-Mei Tsai

  7. Department of Obstetrics and Gynecology, Morsani College of Medicine, University of South Florida, 12901 Bruce B Downs Blvd., MDC48, Tampa, FL, 33612, USA

    S. Joseph Huang

Authors
  1. Nari Kay
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Chun-Yen Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Li-Yen Shiu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ya-Chun Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yu Chang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jau-Ling Suen
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Eing-Mei Tsai
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. S. Joseph Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Eing-Mei Tsai or S. Joseph Huang.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kay, N., Huang, CY., Shiu, LY. et al. The Effects of Anti-TGF-β1 on Epithelial–Mesenchymal Transition in the Pathogenesis of Adenomyosis. Reprod. Sci. 27, 1698–1706 (2020). https://doi.org/10.1007/s43032-020-00139-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s43032-020-00139-0

Keywords

Search

Navigation