The role of growth factors and pseudocapsule in the pathogenesis of uterine fibroids
- Authors: Malysheva O.V.1, Polenov N.I.1, Yarmolinskaya M.I.1
-
Affiliations:
- The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott
- Issue: Vol 74, No 3 (2025)
- Pages: 25-34
- Section: Original study articles
- Submitted: 14.04.2025
- Accepted: 28.05.2025
- Published: 23.07.2025
- URL: https://journals.eco-vector.com/jowd/article/view/678552
- DOI: https://doi.org/10.17816/JOWD678552
- EDN: https://elibrary.ru/DLHCUR
- ID: 678552
Cite item
Abstract
BACKGROUND: Currently, many issues of the pathogenesis of uterine fibroids remain poorly studied, in particular, those related to the role of growth factors in the formation of these neoplasms. In addition, the issue of the role played by the pseudocapsule of the node in tumor growth has not been resolved.
AIM: The aim of this study was to evaluate the expression of growth factor genes TGFB1, TGFB 3, TGFBR2, FGF2, FGFR2, IGF1, and IGF1R in myomatous nodes, pseudocapsule and myometrium in patients with uterine fibroids.
METHODS: The study analyzed a collection of tissues (myometrium, node fragments, pseudocapsule) obtained from patients with uterine fibroids who were examined and treated at the Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott (Saint Petersburg, Russia). The samples were used to determine relative expressions of the TGFB1, TGFB3, TGFBR2, FGF2, FGFR2, IGF1, and IGF1R genes using real-time reverse transcription polymerase chain reaction.
RESULTS: In general, myomatous nodes are characterized by hyperexpression of a number of growth factors genes, such as TGFB1, TGFB3, and IGF1, but tumors are heterogeneous in this indicator. Increased expression of one or two genes encoding ligands of these signaling pathways was detected in 56% of myomatous nodes. In addition, we found hyperexpression of the TGFB1, TGFB3, and IGF1 genes in the pseudocapsule of some nodes.
CONCLUSION: Hyperexpression of certain growth factors may occur in both the nodes and fibroid pseudocapsules. Presumably, in some cases, the pseudocapsule is capable of independently producing growth factors that can stimulate the proliferation of fibroid node cells and the formation of an extracellular matrix therein. The data obtained indicate the ambiguity of the generally accepted recommendations on the need to preserve the pseudocapsule of the myomatous node during myomectomy, which undoubtedly requires further research.
Keywords
Full Text

About the authors
Olga V. Malysheva
The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott
Email: omal99@mail.ru
ORCID iD: 0000-0002-8626-5071
SPIN-code: 1740-2691
Cand. Sci. (Biology)
Russian Federation, Saint PetersburgNikolai I. Polenov
The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott
Email: polenovdoc@mail.ru
ORCID iD: 0000-0001-8575-7026
SPIN-code: 9387-1703
Scopus Author ID: 57221965664
MD, Cand. Sci. (Medicine)
Russian Federation, Saint PetersburgMaria I. Yarmolinskaya
The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott
Author for correspondence.
Email: m.yarmolinskaya@gmail.com
ORCID iD: 0000-0002-6551-4147
SPIN-code: 3686-3605
MD, Dr. Sci. (Medicine), Professor, Professor of the Russian Academy of Sciences, Honored Scientist of the Russian Federation
Russian Federation, Saint PetersburgReferences
- Mehine M, Kaasinen E, Heinonen H-R, et al. Integrated data analysis reveals uterine leiomyoma subtypes with distinct driver pathways and biomarkers. Proc Natl Acad Sci. 2016;113(5):1315–1320. doi: 10.1073/pnas.1518752113
- Osinovskaya NS, Malysheva OV, Shved Nyu, et al. Frequency and spectrum of MED12 exon 2 mutations in multiple versus solitary uterine leiomyomas from Russian patients. Int J Gynecol Pathol. 2016;35(6):509–515. EDN: YUKAQT doi: 10.1097/PGP.0000000000000255
- Blobe GC, Schiemann WP, Lodish HF. Role of transforming growth factor β in human disease. N Engl J Med. 2000;342(18):1350–1358. doi: 10.1056/NEJM200005043421807
- Otten J, Bokemeyer C, Fiedler W. TGF-β superfamily receptors-targets for antiangiogenic therapy? J Oncol. 2010;2010:1–10. doi: 10.1155/2010/317068
- Arici A, Sozen I. Transforming growth factor-beta3 is expressed at high levels in leiomyoma where it stimulates fibronectin expression and cell proliferation. Fertil Steril. 2000;73(5):1006–1011. doi: 10.1016/s0015-0282(00)00418-0
- Pohlers D, Brenmoehl J, Löffler I, et al. TGF-beta and fibrosis in different organs - molecular pathway imprints. Biochim Biophys Acta. 2009;1792(8):746–756. doi: 10.1016/j.bbadis.2009.06.004
- Lee BS, Nowak RA. Human leiomyoma smooth muscle cells show increased expression of transforming growth factor-beta 3 (TGF beta 3) and altered responses to the antiproliferative effects of TGF beta. J Clin Endocrinol Metab. 2001;86(2):913–920. doi: 10.1210/jcem.86.2.7237
- Helmke BM, Markowski DN, Müller MH, et al. HMGA proteins regulate the expression of FGF2 in uterine fibroids. Mol Hum Reprod. 2011;17(2):135–142. EDN: OANKNJ doi: 10.1093/molehr/gaq083
- Bodner-Adler B, Mayerhofer K, Czerwenka K, et al. The role of fibroblast growth factor 2 in patients with uterine smooth muscle tumors: an immunohistochemical study. Eur J Obstet Gynecol Reprod Biol. 2016;207:62–67. doi: 10.1016/j.ejogrb.2016.10.028
- Fernig DG, Gallagher JT. Fibroblast growth factors and their receptors: an information network controlling tissue growth, morphogenesis and repair. Prog Growth Factor Res. 1994;5(4):353–377. doi: 10.1016/0955-2235(94)00007-8
- Wu X, Blanck A, Olovsson M, et al. Expression of basic fibroblast growth factor (bFGF), FGF receptor 1 and FGF receptor 2 in uterine leiomyomas and myometrium during the menstrual cycle, after menopause and GnRHa treatment. Acta Obstet Gynecol Scand. 2001;80(6):497–504. EDN: YIPBGR doi: 10.1034/j.1600-0412.2001.080006497.x
- Duan C. Specifying the cellular responses to IGF signals: roles of IGF-binding proteins. J Endocrinol. 2002;175(1):41–54. EDN: LRRCED doi: 10.1677/joe.0.1750041
- Yu H, Berkel H. Insulin-like growth factors and cancer. J La State Med Soc. 1999;151(4):218–223.
- Werner H, Roberts CT Jr. The IGFI receptor gene: a molecular target for disrupted transcription factors. Genes Chromosomes Cancer. 2003;36(2):113–120. doi: 10.1002/gcc.10157
- Bezhenar VF, Tsypurdeeva AA, Dolinskiy AK, et al. The experience of a standardized technique of laparoscopic myomectomy. Journal of Obstetrics and Women’s Diseases. 2012;61(4):23–32. EDN: QBGFDX doi: 10.17816/JOWD61423-32
- Polenov NI, Dolgikh MS, Yarmolinskaya MI. Analysis of the effectiveness of laparoscopic myomectomy using a standardized technique. Journal of Obstetrics and Women’s Diseases. 2024;73(5):76–83. EDN: SKGCCD doi: 10.17816/JOWD634591
- Islam MS, Greco S, Janjusevic M, et al. Growth factors and pathogenesis. Best Pract Res Clin Obstet Gynaecol. 2016l;34:25–36. EDN: XTTUXP doi: 10.1016/j.bpobgyn.2015.08.018
- Takao T, Ono M, Yoshimasa Y, et al. A mediator complex subunit 12 gain-of-function mutation induces partial leiomyoma cell properties in human uterine smooth muscle cells. F S Sci. 2022;3(3):288–298. EDN: JINHTE doi: 10.1016/j.xfss.2022.04.002
- Echague C, Malik M, Driggers P, et al. Coenzyme Q-10 reduced the aberrant production of extracellular matrix proteins in uterine leiomyomas through transforming growth factor beta 3. F S Sci. 2024;5(4):342–351. EDN: AZFEUU doi: 10.1016/j.xfss.2024.07.004
- Hoffman PJ, Milliken DB, Gregg LC, et al. Molecular characterization of uterine fibroids and its implication for underlying mechanisms of pathogenesis. Fertil Steril. 2004;82(3):639–649. doi: 10.1016/j.fertnstert.2004.01.047
- Milewska G, Ponikwicka-Tyszko D, Bernaczyk P, et al. Functional evidence for two distinct mechanisms of action of progesterone and selective progesterone receptor modulator on uterine leiomyomas. Fertil Steril. 2024;122(2):341–351. EDN: NOORKQ doi: 10.1016/j.fertnstert.2024.02.046
- Lewis TD, Malik M, Britten J, et al. Ulipristal acetate decreases active TGF-β3 and its canonical signaling in uterine leiomyoma via two novel mechanisms. Fertil Steril. 2019;111(4):806–815.e1. EDN: RUSOAK doi: 10.1016/j.fertnstert.2018.12.026
- Pekonen F, Nyman T, Rutanen EM. Differential expression of keratinocyte growth factor and its receptor in the human uterus. Mol Cell Endocrinol. 1993;95(1–2):43–49. doi: 10.1016/0303-7207(93)90027-h
- Mangrulkar RS, Ono M, Ishikawa M, et al. Isolation and characterization of heparin-binding growth factors in human leiomyomas and normal myometrium. Biol Reprod. 1995;53(3):636–646. doi: 10.1095/biolreprod53.3.636
- Dixon D, He H, Haseman JK. Immunohistochemical localization of growth factors and their receptors in uterine leiomyomas and matched myometrium. Environ Health Perspect. 2000;108(Suppl 5):795–802. doi: 10.1289/ehp.00108s5795
- Wolańska M, Bańkowski E. Fibroblast growth factors (FGF) in human myometrium and uterine leiomyomas in various stages of tumour growth. Biochimie. 2006;88(2):141–146. doi: 10.1016/j.biochi.2005.07.014
- Ivanga M, Labrie Y, Calvo E, et al. Temporal analysis of E2 transcriptional induction of PTP and MKP and downregulation of IGF-I pathway key components in the mouse uterus. Physiol Genomics. 2007;29(1):13–23. doi: 10.1152/physiolgenomics.00291.2005
- Peng L, Wen Y, Han Y, et al. Expression of insulin-like growth factors (IGFs) and IGF signaling: molecular complexity in uterine leiomyomas. Fertil Steril. 2009;91(6):2664–2675. doi: 10.1016/j.fertnstert.2007.10.083
- Martin Chaves EB, Brum IS, Stoll J, et al. Insulin-like growth factor 1 receptor mRNA expression and autophosphorylation in human myometrium and leiomyoma. Gynecol Obstet Invest. 2004;57(4):210–213. doi: 10.1159/000076690
Supplementary files
