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小鼠子宫内膜异位症:建立“最佳适配”小鼠模型面临的挑战与进展

Endometriosis in the Mouse: Challenges and Progress Toward a 'Best Fit' Murine Model.

作者信息

Burns Katherine A, Pearson Amelia M, Slack Jessica L, Por Elaine D, Scribner Alicia N, Eti Nazmin A, Burney Richard O

机构信息

Department of Environmental and Public Health Sciences, University of Cincinnati College of Medicine, Cincinnati, OH, United States.

Department of Clinical Investigation, Madigan Army Medical Center, Tacoma, WA, United States.

出版信息

Front Physiol. 2022 Jan 13;12:806574. doi: 10.3389/fphys.2021.806574. eCollection 2021.

Abstract

Endometriosis is a prevalent gynecologic condition associated with pelvic pain and infertility characterized by the implantation and growth of endometrial tissue displaced into the pelvis via retrograde menstruation. The mouse is a molecularly well-annotated and cost-efficient species for modeling human disease in the therapeutic discovery pipeline. However, as a non-menstrual species with a closed tubo-ovarian junction, the mouse poses inherent challenges as a preclinical model for endometriosis research. Over the past three decades, numerous murine models of endometriosis have been described with varying degrees of fidelity in recapitulating the essential pathophysiologic features of the human disease. We conducted a search of the peer-reviewed literature to identify publications describing preclinical research using a murine model of endometriosis. Each model was reviewed according to a panel of ideal model parameters founded on the current understanding of endometriosis pathophysiology. Evaluated parameters included method of transplantation, cycle phase and type of tissue transplanted, recipient immune/ovarian status, iterative schedule of transplantation, and option for longitudinal lesion assessment. Though challenges remain, more recent models have incorporated innovative technical approaches such as fluorescence imaging and novel hormonal preparations to overcome the unique challenges posed by murine anatomy and physiology. These models offer significant advantages in lesion development and readout toward a high-fidelity mouse model for translational research in endometriosis.

摘要

子宫内膜异位症是一种常见的妇科疾病,与盆腔疼痛和不孕相关,其特征是子宫内膜组织通过逆行月经移位到盆腔并植入和生长。在治疗发现流程中,小鼠是一种分子注释完善且成本效益高的用于模拟人类疾病的物种。然而,作为一种具有封闭输卵管卵巢交界处的非月经物种,小鼠作为子宫内膜异位症研究的临床前模型存在固有挑战。在过去三十年中,已经描述了许多子宫内膜异位症的小鼠模型,它们在重现人类疾病的基本病理生理特征方面具有不同程度的逼真度。我们对同行评审文献进行了检索,以识别描述使用子宫内膜异位症小鼠模型进行临床前研究的出版物。每个模型都根据一组基于当前对子宫内膜异位症病理生理学理解的理想模型参数进行了评估。评估的参数包括移植方法、移植组织的周期阶段和类型、受体免疫/卵巢状态、移植的迭代时间表以及纵向病变评估选项。尽管挑战仍然存在,但最近的模型采用了荧光成像和新型激素制剂等创新技术方法,以克服小鼠解剖学和生理学带来的独特挑战。这些模型在病变发展和读出方面具有显著优势,有助于建立用于子宫内膜异位症转化研究的高保真小鼠模型。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f45b/8794744/0a3538107477/fphys-12-806574-g001.jpg

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