Establishment and comparison of different intrauterine adhesion modelling procedures in rats
Li Sun A B , Siwen Zhang A B , Qiyuan Chang A B and Jichun Tan
A B C
+ Author Affiliations
- Author Affiliations
A Assisted Reproduction Centre, Obstetrics and Gynaecology Department, Shengjing Hospital affiliated to China Medical University, No. 39 Huaxiang Road, Tiexi District, Shenyang 110022, China.
B Key Laboratory of Reproductive Dysfunction Diseases and Fertility Remodelling of Liaoning Province, Shengjing Hospital affiliated to China Medical University, Shenyang 110022, China.
C Corresponding author. Email: tjczjh@163.com
Reproduction, Fertility and Development 31(8) 1360-1368 https://doi.org/10.1071/RD18397
Submitted: 30 September 2018 Accepted: 7 February 2019 Published: 9 April 2019
Abstract
Intrauterine adhesion (IUA) is caused by endometrial damage and leads to the formation of scar fibrosis and repair disorders. We compared four different rat IUA modelling procedures in order to establish a stable animal model suitable for investigating IUA. Twenty female Sprague–Dawley rats were randomly divided into four groups. IUA was induced on one side of each rat uterus by ethanol instillation, heat stripping, mechanical injury or mechanical injury with infection (dual-injury); the other side of the uterus was left intact as a control. After 8 days the rats were sacrificed, their uteri were examined for histomorphology and expression of endometrial markers was checked using immunohistochemistry. All four IUA modelling procedures resulted in visual pathophysiological changes in the rat uterus, including stenosis, congestion and loss of elasticity. Endometrial thinning, shrinkage of glands and formation of fibrotic hyperplasia were also observed. All four procedures resulted in the downregulation of cytokeratin 18 and vimentin expression compared with control tissues, as well as the upregulation of collagen I expression. After mechanical injury and dual-injury the expression of interleukin 6 was significantly increased. Overall, our results suggest that ethanol instillation is the most stable IUA modelling procedure. Mechanical injury reliably yielded inflammatory indicators.
Additional keywords: ethanol instillation, heat stripping, mechanical injury.
References
Al Faraj, A., Sultana Shaik, A., Pureza, M. A., Alnafea, M., and Halwani, R. (2014). Preferential macrophage recruitment and polarization in LPS-induced animal model for COPD: noninvasive tracking using MRI. PLoS One 9, e90829.| Preferential macrophage recruitment and polarization in LPS-induced animal model for COPD: noninvasive tracking using MRI.Crossref | GoogleScholarGoogle Scholar | 24598763PubMed |
Bartel, C., Tichy, A., Schoenkypl, S., Aurich, C., and Walter, I. (2013). Effects of steroid hormones on differentiated glandular epithelial and stromal cells in a three dimensional cell culture model of the canine endometrium. BMC Vet. Res. 9, 86–102.
| Effects of steroid hormones on differentiated glandular epithelial and stromal cells in a three dimensional cell culture model of the canine endometrium.Crossref | GoogleScholarGoogle Scholar | 23618385PubMed |
Catorce, M. N., and Gevorkian, G. (2016). LPS-induced murine neuroinflammation model: main features and suitability for pre-clinical assessment of nutraceuticals. Curr. Neuropharmacol. 14, 155–164.
| LPS-induced murine neuroinflammation model: main features and suitability for pre-clinical assessment of nutraceuticals.Crossref | GoogleScholarGoogle Scholar | 26639457PubMed |
Chen, Y., Liu, L., Luo, Y., Chen, M., Huan, Y., and Fang, R. (2017). Prevalence and impact of chronic endometritis in patients with intrauterine adhesions: a prospective cohort study. J. Minim. Invasive Gynecol. 24, 74–79.
| Prevalence and impact of chronic endometritis in patients with intrauterine adhesions: a prospective cohort study.Crossref | GoogleScholarGoogle Scholar | 27773811PubMed |
Couch, Y., Trofimov, A., Markova, N., Nikolenko, V., Steinbusch, H. W., Chekhonin, V., Schroeter, C., Lesch, K. P., Anthony, D. C., and Strekalova, T. (2016). Low-dose lipopolysaccharide (LPS) inhibits aggressive and augments depressive behaviours in a chronic mild stress model in mice. J. Neuroinflammation 13, 108–125.
| Low-dose lipopolysaccharide (LPS) inhibits aggressive and augments depressive behaviours in a chronic mild stress model in mice.Crossref | GoogleScholarGoogle Scholar | 27184538PubMed |
Dmowski, W. P., and Greenblatt, R. B. (1969). Asherman’s syndrome and risk of placenta accreta. Obstet. Gynecol. 34, 288–299.
| 5816312PubMed |
Foix, A., Bruno, R. O., Davison, T., and Lema, B. (1966). The pathology of postcurettage intrauterine adhesions. Am. J. Obstet. Gynecol. 96, 1027–1033.
| The pathology of postcurettage intrauterine adhesions.Crossref | GoogleScholarGoogle Scholar | 5928449PubMed |
Franczak, A., Wojciechowicz, B., and Kotwica, G. (2013). Novel aspects of cytokine action in porcine uterus–endometrial and myometrial production of estrone (E1) in the presence of interleukin 1β (IL1β), interleukin 6 (IL6) and tumor necrosis factor (TNF α) – in vitro study. Folia Biol. (Krakow) 61, 253–261.
| Novel aspects of cytokine action in porcine uterus–endometrial and myometrial production of estrone (E1) in the presence of interleukin 1β (IL1β), interleukin 6 (IL6) and tumor necrosis factor (TNF α) – in vitro study.Crossref | GoogleScholarGoogle Scholar | 24279177PubMed |
Friedler, S., Margalioth, E. J., Kafka, I., and Yaffe, H. (1993). Incidence of post-abortion intra-uterine adhesions evaluated by hysteroscopy – a prospective study. Hum. Reprod. 8, 442–444.
| Incidence of post-abortion intra-uterine adhesions evaluated by hysteroscopy – a prospective study.Crossref | GoogleScholarGoogle Scholar | 8473464PubMed |
Gargett, C. E., Schwab, K. E., and Deane, J. A. (2016). Endometrial stem/progenitor cells: the first 10 years. Hum. Reprod. Update 22, 137–163.
| 26552890PubMed |
Haeger, J. D., Hambruch, N., Dantzer, V., Hoelker, M., Schellander, K., Klisch, K., and Pfarrer, C. (2015). Changes in endometrial ezrin and cytokeratin 18 expression during bovine implantation and in caruncular endometrial spheroids in vitro. Placenta 36, 821–831.
| Changes in endometrial ezrin and cytokeratin 18 expression during bovine implantation and in caruncular endometrial spheroids in vitro.Crossref | GoogleScholarGoogle Scholar | 26116960PubMed |
Hannan, N. J., Jones, R. L., Critchley, H. O., Kovacs, G. J., Rogers, P. A., Affandi, B., and Salamonsen, L. A. (2004). Coexpression of fractalkine and its receptor in normal human endometrium and in endometrium from users of progestin-only contraception supports a role for fractalkine in leukocyte recruitment and endometrial remodeling. J. Clin. Endocrinol. Metab. 89, 6119–6129.
| Coexpression of fractalkine and its receptor in normal human endometrium and in endometrium from users of progestin-only contraception supports a role for fractalkine in leukocyte recruitment and endometrial remodeling.Crossref | GoogleScholarGoogle Scholar | 15579768PubMed |
Hatta, K., Huang, M. L., Weisel, R. D., and Li, R. K. (2012). Culture of rat endometrial telocytes. J. Cell. Mol. Med. 16, 1392–1396.
| Culture of rat endometrial telocytes.Crossref | GoogleScholarGoogle Scholar | 22551155PubMed |
Hinckley, M. D., and Milki, A. A. (2004). 1000 office-based hysteroscopies prior to in vitro fertilization: feasibility and findings. JSLS 8, 103–107.
| 15119651PubMed |
Hooker, A. B., de Leeuw, R., van de Ven, P. M., Bakkum, E. A., Thurkow, A. L., Vogel, N. E. A., van Vliet, H., Bongers, M. Y., Emanuel, M. H., Verdonkschot, A. E. M., Brolmann, H. A. M., and Huirne, J. A. F. (2017). 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. 107, 1223–1231.e3.
| 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.Crossref | GoogleScholarGoogle Scholar | 28390688PubMed |
Hu, J., Zeng, B., Jiang, X., Hu, L., Meng, Y., Zhu, Y., and Mao, M. (2015). The expression of marker for endometrial stem cell and fibrosis was increased in intrauterine adhesions. Int. J. Clin. Exp. Pathol. 8, 1525–1534.
| 25973037PubMed |
Huberlant, S., Fernandez, H., Vieille, P., Khrouf, M., Ulrich, D., deTayrac, R., and Letouzey, V. (2015). Application of a hyaluronic acid gel after intrauterine surgery may improve spontaneous fertility: a randomized controlled trial in New Zealand White rabbits. PLoS One 10, e0125610.
| Application of a hyaluronic acid gel after intrauterine surgery may improve spontaneous fertility: a randomized controlled trial in New Zealand White rabbits.Crossref | GoogleScholarGoogle Scholar | 25961307PubMed |
Jang, H. Y., Myoung, S. M., Choe, J. M., Kim, T., Cheon, Y. P., Kim, Y. M., and Park, H. (2017). Effects of autologous platelet-rich plasma on regeneration of damaged endometrium in female rats. Yonsei Med. J. 58, 1195–1203.
| Effects of autologous platelet-rich plasma on regeneration of damaged endometrium in female rats.Crossref | GoogleScholarGoogle Scholar | 29047244PubMed |
Jensen, P. A., and Stromme, W. B. (1972). Amenorrhea secondary to puerperal curettage (Asherman’s syndrome). Am. J. Obstet. Gynecol. 113, 150–157.
| Amenorrhea secondary to puerperal curettage (Asherman’s syndrome).Crossref | GoogleScholarGoogle Scholar | 5025872PubMed |
Kaya, C., Sever, N., Cengiz, H., Yildiz, S., Ekin, M., and Yasar, L. (2014). A randomized controlled study of the efficacy of misoprostol and hyaluronic acid in preventing adhesion formation after gynecological surgery: a rat uterine horn model. Eur. J. Obstet. Gynecol. Reprod. Biol. 176, 44–49.
| A randomized controlled study of the efficacy of misoprostol and hyaluronic acid in preventing adhesion formation after gynecological surgery: a rat uterine horn model.Crossref | GoogleScholarGoogle Scholar | 24655554PubMed |
Khrouf, M., Morel, O., Hafiz, A., Chavatte-Palmer, P., and Fernandez, H. (2012). Evaluation of the rabbit as an experimental model for human uterine synechia. J. Hum. Reprod. Sci. 5, 175–180.
| Evaluation of the rabbit as an experimental model for human uterine synechia.Crossref | GoogleScholarGoogle Scholar | 23162356PubMed |
Kuramoto, G., Takagi, S., Ishitani, K., Shimizu, T., Okano, T., and Matsui, H. (2015). Preventive effect of oral mucosal epithelial cell sheets on intrauterine adhesions. Hum. Reprod. 30, 406–416.
| Preventive effect of oral mucosal epithelial cell sheets on intrauterine adhesions.Crossref | GoogleScholarGoogle Scholar | 25475585PubMed |
Li, J., Cen, B., Chen, S., and He, Y. (2016). MicroRNA-29b inhibits TGF-beta1-induced fibrosis via regulation of the TGF-beta1/Smad pathway in primary human endometrial stromal cells. Mol. Med. Rep. 13, 4229–4237.
| MicroRNA-29b inhibits TGF-beta1-induced fibrosis via regulation of the TGF-beta1/Smad pathway in primary human endometrial stromal cells.Crossref | GoogleScholarGoogle Scholar | 27035110PubMed |
Lin, X., Zhang, Y., Pan, Y., He, S., Dai, Y., Zhu, B., Wei, C., Xin, L., Xu, W., Xiang, C., and Zhang, S. (2018). Endometrial stem cell-derived granulocyte-colony stimulating factor attenuates endometrial fibrosis via sonic hedgehog transcriptional activator Gli2. Biol. Reprod. 98, 480–490.
| Endometrial stem cell-derived granulocyte-colony stimulating factor attenuates endometrial fibrosis via sonic hedgehog transcriptional activator Gli2.Crossref | GoogleScholarGoogle Scholar | 29329377PubMed |
Liu, F., Zhu, Z. J., Li, P., and He, Y. L. (2013). Creation of a female rabbit model for intrauterine adhesions using mechanical and infectious injury. J. Surg. Res. 183, 296–303.
| Creation of a female rabbit model for intrauterine adhesions using mechanical and infectious injury.Crossref | GoogleScholarGoogle Scholar | 23199550PubMed |
Lo, S. T., Ramsay, P., Pierson, R., Manconi, F., Munro, M. G., and Fraser, I. S. (2008). Endometrial thickness measured by ultrasound scan in women with uterine outlet obstruction due to intrauterine or upper cervical adhesions. Hum. Reprod. 23, 306–309.
| Endometrial thickness measured by ultrasound scan in women with uterine outlet obstruction due to intrauterine or upper cervical adhesions.Crossref | GoogleScholarGoogle Scholar | 18083747PubMed |
Mutlu, L., Hufnagel, D., and Taylor, H. S. (2015). The endometrium as a source of mesenchymal stem cells for regenerative medicine. Biol. Reprod. 92, 138–160.
| The endometrium as a source of mesenchymal stem cells for regenerative medicine.Crossref | GoogleScholarGoogle Scholar | 25904012PubMed |
Römer, T., Müller, J., and Foth, D. (2000). Hydrothermal ablation. A new simple method for coagulating endometrium in patients with therapy-resistant recurring hypermenorrhea. Contrib. Gynecol. Obstet. 20, 154–160.
| 11791278PubMed |
Santamaria, X., Isaacson, K., and Simón, C. (2018). Asherman’s syndrome: it may not be all our fault. Hum. Reprod. 33, 1374–1380.
| Asherman’s syndrome: it may not be all our fault.Crossref | GoogleScholarGoogle Scholar |
Valentijn, A. J., Palial, K., Al-Lamee, H., Tempest, N., Drury, J., Von Zglinicki, T., Saretzki, G., Murray, P., Gargett, C. E., and Hapangama, D. K. (2013). SSEA-1 isolates human endometrial basal glandular epithelial cells: phenotypic and functional characterization and implications in the pathogenesis of endometriosis. Hum. Reprod. 28, 2695–2708.
| SSEA-1 isolates human endometrial basal glandular epithelial cells: phenotypic and functional characterization and implications in the pathogenesis of endometriosis.Crossref | GoogleScholarGoogle Scholar | 23847113PubMed |
van Hoogenhuijze, N. E., Torrance, H. L., Mol, F., Laven, J. S. E., Scheenjes, E., Traas, M. A. F., Janssen, C., Cohlen, B., Teklenburg, G., de Bruin, J. P., et al. (2017). Endometrial scratching in women with implantation failure after a first IVF/ICSI cycle; does it lead to a higher live birth rate? The SCRaTCH study: a randomized controlled trial (NTR 5342). BMC Womens Health 17, 47–54.
| Endometrial scratching in women with implantation failure after a first IVF/ICSI cycle; does it lead to a higher live birth rate? The SCRaTCH study: a randomized controlled trial (NTR 5342).Crossref | GoogleScholarGoogle Scholar | 28732531PubMed |
Wang, X., Ma, N., Sun, Q., Huang, C., Liu, Y., and Luo, X. (2017). Elevated NF-kappaB signaling in Asherman syndrome patients and animal models. Oncotarget 8, 15399–15406.
| Elevated NF-kappaB signaling in Asherman syndrome patients and animal models.Crossref | GoogleScholarGoogle Scholar | 28148903PubMed |
Watson, E. D., Aubrey, E. S., Zanecosky, H. G., and Sertich, P. L. (1992). Isolation and culture of glandular epithelial and stromal cells from the endometrium of mares. J. Reprod. Fertil. 95, 269–275.
| Isolation and culture of glandular epithelial and stromal cells from the endometrium of mares.Crossref | GoogleScholarGoogle Scholar | 1625242PubMed |
Xiao, L., Song, Y., Huang, W., Yang, S., Fu, J., Feng, X., and Zhou, M. (2017). Expression of SOX2, NANOG and OCT4 in a mouse model of lipopolysaccharide-induced acute uterine injury and intrauterine adhesions. Reprod. Biol. Endocrinol. 15, 14–25.
| Expression of SOX2, NANOG and OCT4 in a mouse model of lipopolysaccharide-induced acute uterine injury and intrauterine adhesions.Crossref | GoogleScholarGoogle Scholar |
Xiao, H. B., Sui, G. G., Lu, X. Y., and Sun, Z. L. (2018). Elevated levels of ADMA are associated with lower DDAH2 and higher PRMT1 in LPS-induced endometritis rats. Inflammation 41, 299–306.
| Elevated levels of ADMA are associated with lower DDAH2 and higher PRMT1 in LPS-induced endometritis rats.Crossref | GoogleScholarGoogle Scholar | 29119338PubMed |
Xu, H. L., Xu, J., Shen, B. X., Zhang, S. S., Jin, B. H., Zhu, Q. Y., ZhuGe, D. L., Wu, X. Q., Xiao, J., and Zhao, Y. Z. (2017a). Dual regulations of thermosensitive heparin-poloxamer hydrogel using epsilon-polylysine: bioadhesivity and controlled KGF release for enhancing wound healing of endometrial injury. ACS Appl. Mater. Interfaces 9, 29580–29594.
| Dual regulations of thermosensitive heparin-poloxamer hydrogel using epsilon-polylysine: bioadhesivity and controlled KGF release for enhancing wound healing of endometrial injury.Crossref | GoogleScholarGoogle Scholar | 28809108PubMed |
Xu, H. L., Xu, J., Zhang, S. S., Zhu, Q. Y., Jin, B. H., ZhuGe, D. L., Shen, B. X., Wu, X. Q., Xiao, J., and Zhao, Y. Z. (2017b). Temperature-sensitive heparin-modified poloxamer hydrogel with affinity to KGF facilitate the morphologic and functional recovery of the injured rat uterus. Drug Deliv. 24, 867–881.
| Temperature-sensitive heparin-modified poloxamer hydrogel with affinity to KGF facilitate the morphologic and functional recovery of the injured rat uterus.Crossref | GoogleScholarGoogle Scholar | 28574291PubMed |
Xu, X. X., Cao, L. B., Wang, Z., Xu, Z., Zhang, B. Q., Wu, S. L., Qi, S. S., Yan, L., and Chen, Z. J. (2018). Creation of a rabbit model for intrauterine adhesions using electrothermal injury. J. Zhejiang Univ. Sci. B 19, 383–389.
| Creation of a rabbit model for intrauterine adhesions using electrothermal injury.Crossref | GoogleScholarGoogle Scholar | 29732749PubMed |
Yaffe, H., Ron, M., and Polishuk, W. Z. (1978). Amenorrhea, hypomenorrhea, and uterine fibrosis. Am. J. Obstet. Gynecol. 130, 599–601.
| Amenorrhea, hypomenorrhea, and uterine fibrosis.Crossref | GoogleScholarGoogle Scholar | 564609PubMed |
Yang, H., Wu, S., Feng, R., Huang, J., Liu, L., Liu, F., and Chen, Y. (2017). Vitamin C plus hydrogel facilitates bone marrow stromal cell-mediated endometrium regeneration in rats. Stem Cell Res. Ther. 8, 267–277.
| Vitamin C plus hydrogel facilitates bone marrow stromal cell-mediated endometrium regeneration in rats.Crossref | GoogleScholarGoogle Scholar | 29157289PubMed |
Zakaria, R., Wan Yaacob, W. M., Othman, Z., Long, I., Ahmad, A. H., and Al-Rahbi, B. (2017). Lipopolysaccharide-induced memory impairment in rats: a model of Alzheimer’s disease. Physiol. Res. 66, 553–565.
| 28406691PubMed |
Zupi, E., Centini, G., and Lazzeri, L. (2015). Asherman syndrome: an unsolved clinical definition and management. Fertil. Steril. 104, 1380–1381.
| Asherman syndrome: an unsolved clinical definition and management.Crossref | GoogleScholarGoogle Scholar | 26484781PubMed |
