An Experimental Murine Model of Asherman’s Syndrome: Characterization of Endometrial Fibrosis and Functional Assessment of Fertility Using a Novel Anesthesia Approach
Student Research in Translational Medicine,
Vol. 7 (2025),
1 March 2025
,
Page 1-9
https://doi.org/10.22037/srtm.v7.51463
Abstract
Background and Aim: Intrauterine adhesion (IUA), or Asherman’s syndrome, is a significant gynecological disorder characterized by fibrous scar tissue formation within the uterine cavity. It commonly results from endometrial trauma following surgical procedures or infection and is a major cause of menstrual abnormalities, including hypomenorrhea or amenorrhea, as well as infertility. Progress in developing effective therapies has been limited by the lack of
well- characterized preclinical models that adequately assess both structural damage and fertility outcomes. This study aimed to establish and characterize a reproducible mouse model of IUA that recapitulates both the pathological and functional features of the human disease.
Methods: Female NMRI mice underwent mechanical endometrial injury via uterine scraping. A balanced anesthetic protocol consisting of ketamine/ xylazine induction followed by isoflurane maintenance was used to ensure stable, long-duration anesthesia with minimal distress. Histological, molecular, and fertility assessments were performed to evaluate endometrial damage and reproductive function.
Results: Histopathological analysis demonstrated a significant reduction in endometrial thickness (p = 0.008) and gland number (p = 0.024), accompanied by extensive fibrosis
(p = 0.016), as evidenced by H&E and Masson’s trichrome staining. Molecular analyses revealed marked upregulation of type I collagen (Col-1) (p = 0.048) and α-smooth muscle actin (α-SMA) (p = 0.033), confirming a fibrotic phenotype. Functionally, fertility was severely impaired, as indicated by a substantial decrease in the number of implanted fetuses
(p = 0.011) and the live birth rate (p = 0.004) in the IUA group compared with controls.
Conclusion: This murine model reproduces the structural, molecular, and functional abnormalities associated with IUA and provides a robust platform for investigating endometrial fibrosis and evaluating novel therapeutic strategies.
- Asherman’s syndrome
- Intrauterine adhesion
- Mouse model
- Fibrosis
- Fertility
- Anesthesia
How to Cite
References
1. Yu D, Wong YM, Cheong Y, Xia E, Li TC. Asherman syndrome--one century later. Fertil Steril. 2008 Apr;89(4):759–79.
2. Hooker AB, de Leeuw R, van de Ven PM, Bakkum EA, Thurkow AL, Vogel NEA, et al. Prevalence of intrauterine adhesions after the application of hyaluronic acid gel after dilatation and curettage in women with at least one previous curettage: short-term outcomes of a multicenter, prospective randomized controlled trial. Fertil Steril. 2017 May;107(5):1223-1231.e3.
3. Toma LM, Socolov D, Matei D, Anton S, Balan R, Anton E, et al. Intrauterine Adhesions and Asherman Syndrome: A Retrospective Dive into Predictive Risk Factors, Diagnosis, and Surgical Perspectives. Diagnostics. 2025;15(8).
4. Myers EM, Hurst BS. Comprehensive management of severe Asherman syndrome and amenorrhea. Fertil Steril. 2012 Jan;97(1):160–4.
5. Capella-Allouc S, Morsad F, Rongières-Bertrand C, Taylor S, Fernandez H. Hysteroscopic treatment of severe Asherman’s syndrome and subsequent fertility. Hum Reprod. 1999 May;14(5):1230–3.
6. Liu L, Yang H, Guo Y, Yang G, Chen Y. The impact of chronic endometritis on endometrial fibrosis and reproductive prognosis in patients with moderate and severe intrauterine adhesions: a prospective cohort study. Fertil Steril. 2019 May;111(5):1002-1010.e2.
7. Xi J, Pan Y, Jin C, Liu J, Cheng J, Xu B. Evaluation of different rat models intrauterine adhesion models and improvement of the technique for their establishment. Exp Anim. 2023 May 17;72(2):274–84.
8. Liu PC, Song YT, Zhao LM, Jiang YL, Hu JG, Dong L, et al. Establishment and comparison of different procedures for modeling intrauterine adhesion in rats: A preliminary study. Heliyon. 2024 Feb 15;10(3):e25365.
9. Liu D, Yuan L, Xu F, Ma Y, Zhang H, Jin Y, et al. Interleukin-33 promotes intrauterine adhesion formation in mice through the mitogen-activated protein kinase signaling pathway. Communications Biology. 2024 Aug 20;7(1):1022.
10. Xu XX, Cao LB, Wang Z, Xu Z, Zhang BQ, Wu SL, et al. Creation of a rabbit model for intrauterine adhesions using electrothermal injury. J Zhejiang Univ Sci B. 2018 May;19(5):383–9.
11. Feng Q, Gao B, Zhao X, Huang H, Yi S, Zou L, et al. Establishment of an animal model of intrauterine adhesions after surgical abortion and curettage in pregnant rats. Ann Transl Med. 2020 Feb;8(4):56.
12. Rasouli-Saravani A, Ghanbarian H, Ramezani-Tehrani F, Mosaffa N, Ghaffari-Khaligh S, Ghambari-Mohammadi N, et al. Human amniotic fluidic derived-extracellular vesicles enriched by miR-29 ameliorate endometrial fibrosis and promote repair of damaged endometrium in an experimental model of intrauterine adhesion. Biochem Biophys Res Commun. 2026 Jan 29;806:153344.
13. Liu L, Chen G, Chen T, Shi W, Hu H, Song K, et al. si-SNHG5-FOXF2 inhibits TGF-β1-induced fibrosis in human primary endometrial stromal cells by the Wnt/β-catenin signalling pathway. Stem Cell Res Ther. 2020 Nov 11;11(1):479.
14. Xu C, Bao M, Fan X, Huang J, Zhu C, Xia W. EndMT: New findings on the origin of myofibroblasts in endometrial fibrosis of intrauterine adhesions. Reprod Biol Endocrinol. 2022 Jan 7;20(1):9.
15. Yang J, Ren L, Gu X, Wang L, Cui J. Microfibrillar-associated protein 5 promotes TGF-β1-induced endometrial epithelial fibrosis in intrauterine adhesion. Biol Reprod. 2025 Oct 27;ioaf242.
16. Liu F, Zhu ZJ, Li P, He YL. Creation of a female rabbit model for intrauterine adhesions using mechanical and infectious injury. J Surg Res. 2013 Jul;183(1):296–303.
17. Guo LP, Chen LM, Chen F, Jiang NH, Sui L. Smad signaling coincides with epithelial-mesenchymal transition in a rat model of intrauterine adhesion. Am J Transl Res. 2019;11(8):4726–37.
18. Yang H, Zhang W, Fang J, Tang Z, Zhou Y, Hu H, et al. Intrauterine infusion of platelet-rich plasma improves fibrosis by transforming growth factor beta 1/Smad pathway in a rat intrauterine adhesion model. Reprod Biol. 2024 Jun;24(2):100882.
19. Li B, Zhang Q, Sun J, Lai D. Human amniotic epithelial cells improve fertility in an intrauterine adhesion mouse model. Stem Cell Res Ther. 2019 Aug 14;10(1):257.
20. Virgilio T, Latino I, Pizzichetti C, Chahine K, Capucetti A, Detotto C, et al. Impact of prolonged isoflurane or ketamine–xylazine anesthesia with or without buprenorphine and oxygen on mouse vitals and immune responses. Lab Animal. 2025 Oct 1;54(10):270–7.
21. Blevins CE, Celeste NA, Marx JO. Effects of Oxygen Supplementation on Injectable and Inhalant Anesthesia in C57BL/6 Mice. J Am Assoc Lab Anim Sci. 2021 May 1;60(3):289–97.
22. Mechelinck M, Kupp C, Krüger JC, Habigt MA, Helmedag MJ, Tolba RH, et al. Oxygen inhalation improves postoperative survival in ketamine-xylazine anaesthetised rats: An observational study. PLoS One. 2019;14(12):e0226430.
23. David EM, Pacharinsak C, Jampachaisri K, Hagan L, Marx JO. Use of Ketamine or Xylazine to Provide Balanced Anesthesia with Isoflurane in C57BL/6J Mice. J Am Assoc Lab Anim Sci. 2022 Sep 1;61(5):457–67.
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