Expression of epithelial–mesenchymal transition markers in different forms of ectopic pregnancy
Danilov A.A., Kozachenko A.V., Badlaeva A.S., Asaturova A.V.
Objective: To investigate the role of epithelial-mesenchymal transition (EMT) in different forms of ectopic pregnancy by analyzing the expression of EMT markers.
Materials and methods: Forty-nine patients who underwent surgical treatment for ectopic pregnancies in various locations were included in the study: cervical/cervico-isthmic (n=20), tubal (n=12), and cesarean scar (n=17). Immunohistochemistry was used to assess EMT marker expression in the intermediate trophoblast, syncytiotrophoblast, and cytotrophoblast of the removed gestational sac, as well as in endometrial/endocervical curettage specimens. Uterine cavity curettage specimens from ten women with normal early pregnancies were used as controls. Statistical analysis was performed using GraphPad Prism 9.3.1 (Dotmatics, USA). The Shapiro–Wilk and Kruskal–Wallis tests were used, with statistical significance set at p<0.05.
Results: Compared with patients with tubal pregnancies, those with rare forms of ectopic pregnancy had a higher number of previous pregnancies, deliveries (including operative deliveries), and abortions. Pre- and post-surgical β-hCG levels were also significantly higher in the rare ectopic pregnancy group. The EMT marker E-cadherin showed comparable expression in the intermediate trophoblast of cervical and normal pregnancies (p>0.5), but higher expression in the cytotrophoblast of patients with cervical pregnancies (p<0.04). The lowest E-cadherin expression was detected in the cytotrophoblasts of tubal pregnancies. In ectopic pregnancies, β-catenin expression predominated in the intermediate trophoblast (p<0.0001), whereas in intrauterine pregnancies, it predominated in the cytotrophoblast.
Conclusion: EMT is involved in the development of ectopic pregnancy, with a specific pattern of EMT marker expression varying depending on the location of the gestational sac.
Authors' contributions: Kozachenko A.V. – final editing of the manuscript; Danilov A.A. – design of the study, material collection, statistical analysis, drafting of the manuscript; Asaturova A.V., Badlaeva A.S. – immunohistochemical study, analysis of the results.
Conflicts of interest: The authors have no conflicts of interest to declare.
Funding: There was no funding for this study.
Ethical Approval: The study was reviewed and approved by the Research Ethics Committee of the V.I. Kulakov NMRC for OG&P, Ministry of Health of Russia.
Patient Consent for Publication: All patients provided informed consent for the publication of their data.
Authors' Data Sharing Statement: The data supporting the findings of this study are available upon request from the corresponding author after approval from the principal investigator.
For citation: Danilov A.A., Kozachenko A.V., Badlaeva A.S., Asaturova A.V. Expression of
epithelial-mesenchymal transition markers in different forms of ectopic pregnancy.
Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2026; (4): 87-95 (in Russian)
https://dx.doi.org/10.18565/aig.2026.377
Keywords
ectopic pregnancy
cervical pregnancy
cervico-isthmic pregnancy
cesarean scar pregnancy
E-cadherin
β-catenin
References
- Гапонова А.В., Родин С., Мазина А.А., Волчков П.Ю. Эпителиально-мезенхимальный переход: злокачественная прогрессия и перспективы противоопухолевой терапии. Acta Naturae. 2020; 12(3): 4-23. [Gaponova A.V., Rodin S., Mazina A.A., Volchkov P.Yu. Epithelial-mesenchymal transition: malignant progression and prospects of anticancer therapy. Acta Naturae. 2020; 12(3): 4-23 (in Russian)].
- Шварев Е.Г., Зоева А.Р., Зайцев И.В. Эпителиально-мезенхимальный переход как важный этап формирования патологических пролиферативных заболеваний матки. Российский вестник акушера-гинеколога. 2025; 25(4): 37 43. [Shvarev E.G., Zoeva A.R., Zaitsev I.V. Epithelial-mesenchymal transition as an important stage in the formation of pathological proliferative diseases of the uterus. Russian Bulletin of Obstetrician-Gynecologist. 2025; 25(4): 37 43 (in Russian)]. https://dx.doi.org/10.17116/rosakush20252504137
- Akhurst R.J. From shape-shifting embryonic cells to oncology: The fascinating history of epithelial mesenchymal transition. Semin. Cancer Biol. 2023; 96: 100-14. https://dx.doi.org/10.1016/j.semcancer.2023.10.003
- Вишнякова П.А., Тарасова Н.В., Володина М.А., Марей М.В., Ходжаева З.С., Кан Н.Е., Высоких М.Ю. Эпителиально-мезенхимальный переход в плаценте при преэклампсии. Акушерство и гинекология. 2016; 12: 53-7. [Vishnyakova P.A., Tarasova N.V., Volodina M.A., Marei M.V., Khodzhaeva Z.S., Kan N.E., Vysokikh M.Yu. Placental epithelial-mesenchymal transition in preeclampsia. Obstetrics and Gynecology. 2016; (12): 53-7 (in Russian)]. https://dx.doi.org/10.18565/aig.2016.12.53-7
- Bilyk O., Coatham M., Jewer M., Postovit L.M. Epithelial-to-mesenchymal transition in the female reproductive tract: from normal functioning to disease pathology. Front. Oncol. 2017; 7: 145. https://dx.doi.org/10.3389/fonc.2017.00145
- Panelli D.M., Phillips Flanagan C.H., Brady P.C. Incidence, diagnosis and management of tubal and nontubal ectopic pregnancies. Fertil. Res. Pract. 2015; 1: 15. http://dx.doi.org/10.1186/s40738-015-0008-z
- Gao L., Chen H., Liu J., Wang M., Lin F., Yang G. et al. Extravillous trophoblast invasion and decidualization in cesarean scar pregnancies. Acta Obstet. Gynecol. Scand. 2022; 101(10): 1120-8. https://dx.doi.org/10.1111/aogs.14435
- Liu N., Peng S.M., Zhan G.X., Yu J., Wu W.M., Gao H. et al. Human chorionic gonadotropin β regulates epithelial-mesenchymal transition and metastasis in human ovarian cancer. Oncol. Rep. 2017; 38(3): 1464-72. https://dx.doi.org/10.3892/or.2017.5818
- Kawamata F., Nishihara H., Homma S., Kato Y., Tsuda M., Konishi Y. et al. Chorionic gonadotropin β modulates epithelial-mesenchymal transition in colorectal carcinoma metastasis. Am. J. Pathol. 2018; 118(1): 204-15. https://dx.doi.org/10.1016/j.ajpath.2017.08.034
- Ishida M., Takebayashi A., Kimura F., Nakamura A., Kitazawa J., Morimune A. et al. Induction of the epithelial-mesenchymal transition in the endometrium by chronic endometritis in infertile patients. PLoS One. 2021; 16(4): e0249775. https://dx.doi.org/10.1371/journal.pone.0249775
- Kahata K., Dabras M.S., Moustakas A. TGF-beta family signaling in epithelial differentiation and epithelial-mesenchymal transition. Cold Spring Harb. Perspect. Biol. 2018; 10(1): a022194. https://dx.doi.org/10.1101/cshperspect.a022194
- Song P., Gao Z., Bao Y., Chen L., Hang Y., Liu Y. et al. Wnt/beta-catenin signaling pathway in cancerogenesis and cancer therapy. J. Hematol. Oncol. 2024; 17(1): 46. https://dx.doi.org/10.1186/s13045-024-01563-4
- Jiang H., Yang X.Y., Zhu W.J. Network of E-cadherin, β1 integrin, and local adhesion kinase in the pathogenesis of tubal pregnancy. Gynecol. Endocrinol. 2019; 35(4): 346-50. https://dx.doi.org/10.1080/09513590.2018.1528578
- Flanagan H., Lin C.J., Campbell L.L., Horner P., Horne A.W., Spears N. Ectopic pregnancy and epithelial to mesenchymal transition: is there a link? Reproduction. 2020; 161(3): V11-4. https://dx.doi.org/10.1530/REP-20-0542
- Han Q., Zheng L., Liu Z., Luo J., Chen J., Yan J. Expression of β-catenin in human trophoblast and its role in placenta accreta and placenta previa. J. Int. Med. Res. 2016; 47(1): 206-14. https://dx.doi.org/10.1177/0300060518799265
- Liu Y., Li P., Liao J., Rao M., Peng L., Gan H. et al. Decreased RSPO3 and beta-catenin in preeclampsia: correlation with blood pressure and pregnancy outcomes. Med. Sci. Monit. 2024; 30: e945848. https://dx.doi.org/10.12659/MSM.945848
- DaSilva-Arnold S., James J.L., Al-Khan A., Zamudio S., Illsley N.P. Differentiation of first-trimester cytotrophoblast to extravillous trophoblast involves epithelial-mesenchymal transition. Placenta. 2015; 36(12): 1412-8. https://dx.doi.org/10.1016/j.placenta.2015.10.013
- Chronopoulou E., Koika V., Tsiveriotis K., Stefanidis K., Kalogeropoulos S., Georgopoulos N. et al. Wnt4, Wnt6 and beta-catenin expression in human placental tissue – is there a link with first trimester miscarriage? Results from a pilot study. Reprod. Biol. Endocrinol. 2022; 20(1): 51. https://dx.doi.org/10.1186/s12958-022-00923-4
Received 16.12.2025
Accepted 19.03.2026
About the Authors
Andrey A. Danilov, PhD student at the Gynecological Department, V.I. Kulakov NMRC for OG&P, Ministry of Health of Russia, 117997, Russia, Moscow, Ac. Oparin str., 4,andreydanilov2018@gmail.com, https://orcid.org/0009-0009-1959-2548
Andrey V. Kozachenko, Dr. Med. Sci., Senior Researcher at the Gynecological Department, V.I. Kulakov NMRC for OG&P, Ministry of Health of Russia, 117997, Russia, Moscow, Ac. Oparin str., 4, a_kozachenko@oparina4.ru, https://orcid.org/0000-0002-5573-6694
Alina S. Badlaeva, PhD, Senior Researcher at the 1st Pathoanatomical Department, V.I. Kulakov NMRC for OG&P, Ministry of Health of Russia, 117997, Russia, Moscow,
Ac. Oparin str., 4, a_badlaeva@oparina4.ru, https://orcid.org/0000-0001-5223-9767
Alexandra V. Asaturova, Dr. Med. Sci., Head of the 1st Department of Anatomical Pathology, V.I. Kulakov NMRC for OG&P, Ministry of Health of Russia, 117997, Russia, Moscow, Ac. Oparin str., 4, a_asaturova@oparina4.ru, https://orcid.org/0000-0001-8739-5209
Similar Articles
