Research question

Do uterine procedures potentially disrupting the endometrial–myometrial interface (EMI) induce adenomyosis?

Design

Six prospective, randomized controlled experiments were conducted involving a total of 106 female BALB/c and 12 female C57BL/6 mice. The incidence of adenomyosis was evaluated in these two strains of mouse after mechanically induced EMI disruption (EMID), or thermally induced EMID using electrocoagulation of different intensities. Finally, the incidence was evaluated in mice that had received perioperative administration of aprepitant (an NK1R inhibitor), propranolol (a beta-blocker) or vehicle. Body weight, hot plate latency and grade of myometrial infiltration were evaluated. Histology, immunohistochemistry and histochemistry analyses were also performed.

Results

Mechanical injury to the EMI caused EMID. Adenomyosis developed in the majority of mice in the EMID groups 3 months after mechanically induced EMID but did not develop in the control group (83.3% in C57BL/6 mice, P = 0.015; 100% in BALB/c mice, P = 0.0002). With thermally induced EMID, adenomyosis was found in 30% of the EMID mice 10 weeks later, but the incidence increased to 66.7% if the extent of EMID damage was increased. In mice with perioperative administration of aprepitant or propranolol, the incidence of adenomyosis was reduced from 100% to 58.3% (both P = 0.00034).

Conclusions

This study provides the first piece of experimental evidence that EMID resulting from iatrogenic uterine procedures can substantially increase the risk of developing adenomyosis, with the risk in proportion to the severity of disruption. More intriguingly, perioperative administration of an NK1R antagonist or beta-blocker significantly reduced the risk of developing adenomyosis.

中文翻译：

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由机械或热诱导的子宫内膜 - 肌层界面破坏引起的小鼠子宫腺肌病及其可能的预防。

研究问题

子宫手术是否可能破坏子宫内膜 - 肌层界面 (EMI) 诱发子宫腺肌病？

设计

进行了六个前瞻性、随机对照实验，涉及总共 106 只雌性 BALB/c 和 12 只雌性 C57BL/6 小鼠。在机械诱导 EMI 破坏 (EMID) 或使用不同强度电凝的热诱导 EMID 后，评估了这两种小鼠品系的子宫腺肌病的发生率。最后，在围手术期接受阿瑞匹坦（一种 NK1R 抑制剂）、普萘洛尔（一种 β 受体阻滞剂）或载体的小鼠中评估了发病率。评估体重、热板潜伏期和子宫肌层浸润程度。还进行了组织学、免疫组织化学和组织化学分析。

结果

EMI的机械损伤引起EMID。机械诱导 EMID 3 个月后，大多数 EMID 组小鼠出现子宫腺肌病，但对照组未出现子宫腺肌病（C57BL/6 小鼠为 83.3%，P =  0.015；BALB/c 小鼠为 100%，P =  0.0002） . 对于热诱导的 EMID，10 周后在 30% 的 EMID 小鼠中发现子宫腺肌病，但如果 EMID 损伤程度增加，发生率会增加到 66.7%。在围手术期给予阿瑞匹坦或普萘洛尔的小鼠中，子宫腺肌病的发生率从 100% 降至 58.3%（均P =  0.00034）。

结论

这项研究提供了第一条实验证据，证明医源性子宫手术导致的 EMID 会显着增加发生子宫腺肌病的风险，风险与破坏的严重程度成正比。更有趣的是，围手术期使用 NK1R 拮抗剂或 β 受体阻滞剂可显着降低发生子宫腺肌病的风险。