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在月经周期小鼠模型(小家鼠)中诱导子宫内膜异位症:一种转化型动物疾病模型

Induction of Endometriosis in a Menstruating Mouse Model (Mus musculus): A Translational Animal Disease Model.

作者信息

Howe Christina A, Coté John J, Stoos Catherine T, Hallgren Jodi J, Bredehoeft Marley R, Gelineau-van Waes Janee B

机构信息

1Research Compliance, Creighton University School of Medicine, Omaha, Nebraska.

2Department of Obstetrics and Gynecology, CHI Health, Creighton University Medical Center, Omaha, Nebraska.

出版信息

J Am Assoc Lab Anim Sci. 2025 May 1;64(4):1-15. doi: 10.30802/AALAS-JAALAS-24-160.

Abstract

Improved animal models of endometriosis are needed to accurately represent the pathophysiology of human disease and identify new therapeutic targets that do not compromise fertility. There is tremendous heterogeneity among published rodent models of endometriosis, and the etiology and pathogenesis of endometriosis remain undetermined. The vast majority of endometriosis is found in menstruating women; however, no published mouse models have induced endometriosis in a menstruating mouse, further limiting our understanding of the disease. Our goal was to develop a novel, translationally relevant mouse model of endometriosis in a menstruating mouse by transplanting donor menstrual endometrium into the peritoneal cavity of menstruating, immunocompetent, intact recipients. We initially compared 4 different experimental groups to optimize implanted menstrual tissue type and method of implantation into intact, normally cycling recipient mice. To further optimize this model, a novel fifth experimental group was compared in which discrete pieces of menstrual donor endometrium were implanted via laparoscopy into menstruating recipient mice. Lesions were confirmed to be endometriosis based on histopathology. The use of laparoscopy to place discrete fragments of menstrual phase endometrium intraabdominally was the most effective method for induction of endometriosis. This method was just as effective when used to induce endometriosis in menstruating recipient mice. Menstruating mice returned to normal estrus cyclicity after induction of disease, which can allow for assessment of therapeutic interventions on fertility. This is a novel translationally relevant mouse model of endometriosis in a menstruating mouse that can be used to explore and elucidate the etiology and pathogenesis of this disease.

摘要

需要改进子宫内膜异位症的动物模型,以准确呈现人类疾病的病理生理学,并确定不影响生育能力的新治疗靶点。已发表的啮齿动物子宫内膜异位症模型存在极大的异质性,且子宫内膜异位症的病因和发病机制仍未明确。绝大多数子宫内膜异位症见于有月经的女性;然而,尚无已发表的小鼠模型能在有月经的小鼠中诱导出子宫内膜异位症,这进一步限制了我们对该疾病的理解。我们的目标是通过将供体月经子宫内膜移植到有月经、具有免疫活性的完整受体小鼠的腹腔中,开发一种新型的、与临床相关的有月经小鼠子宫内膜异位症模型。我们最初比较了4个不同的实验组,以优化植入月经组织的类型和植入完整、正常周期受体小鼠的方法。为了进一步优化该模型,我们比较了一个新的第五实验组,即通过腹腔镜将离散的月经供体子宫内膜碎片植入有月经的受体小鼠体内。根据组织病理学确认病变为子宫内膜异位症。使用腹腔镜将月经周期子宫内膜的离散碎片置于腹腔内是诱导子宫内膜异位症最有效的方法。当用于在有月经的受体小鼠中诱导子宫内膜异位症时,该方法同样有效。诱导疾病后,有月经的小鼠恢复到正常的发情周期,这可以评估对生育能力的治疗干预。这是一种新型的、与临床相关的有月经小鼠子宫内膜异位症模型,可用于探索和阐明该疾病的病因和发病机制。

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