Establishment of an animal model of intrauterine adhesions after surgical abortion and curettage in pregnant rats

Ann Transl Med. 2020 Feb;8(4):56. doi: 10.21037/atm.2020.01.134.

Abstract

Background: Intrauterine adhesion (IUA), also referred to as Asherman syndrome, is a complication with partial or complete adhesion of the uterine cavity due to fibrotic proliferation after endometrial and uterine wall injury of the newly pregnant uterus. Currently, all IUA research models are based on non-pregnant animals which are ill-suited in mimicking its pathogenesis. This study aimed to establish an animal IUA model caused by surgical abortion and curettage in pregnant rats that is more in line with clinical etiology, and to provide a more ideal animal model for further exploration of the pathogenesis and treatment for IUA.

Methods: Fifteen, 13-to-15-day pregnant Sprague-Dawley (SD) rats aged 10 weeks were selected. After incising and removing the embryos, we randomly selected one side of the uterine cavity as the study group (n=15) and scraped it with a curette; the contralateral side of the uterine cavity that underwent no special procedures was used for inclusion in the control group (n=15). Five rats were euthanized and dissected on the 3rd, 7th, and 14th day after surgery respectively. The changes in tissue morphology, the number of endometrial glands, the ratio of endometrial fibrotic area, and the expression level of the transforming growth factor beta (TGF-β) in the endometrium were compared between the 2 groups.

Results: The endometrial granular cell number in the study group on the 7th and 14th day postoperatively was 3.87±0.72 & 2.59±0.90 in each visual field (×100) respectively, which was significantly lower than that of the control group (6.48±0.96 & 7.53±1.10; P<0.05). The ratio of the endometrial stromal fibrotic area in the study group was significantly higher than that of the control group post-operatively on the 3rd day (0.0974±0.0430 vs. 0.0584±0.05110), 7th day (0.1551±0.0348 vs. 0.0328±0.0152), and 14th day (0.1518±0.0477 vs. 0.0311±0.0128) (P<0.05). The endometrial TGF-β expression in the study group was positive on the 14th day postoperatively while weakly expressed in the control group, and the integrated optical density (IOD) value (5,608.8±2,887.3) was higher than that of the control group (388.3±98.6) (P<0.05). The endometrial TGF-β expression in the study group and control group was relatively weak on the 3rd and 7th day after surgery, and there was no significant difference when compared with that of the control group (P>0.05).

Conclusions: The establishment of an animal model of IUA after surgical abortion and curettage in pregnant rats was successful and is thus feasible for further studies; the model may be a more effective mimic for the generation of human IUA.

Keywords: Intrauterine adhesions (IUAs); animal models; endometrial fibrosis; pathogenesis; pregnant rats.