Department of Obstetrics, Gynecology and Reproductive Biology, Michigan State University, Grand Rapids, Michigan.
Cell and Molecular Biology Program, Michigan State University, East Lansing, Michigan.
Semin Reprod Med. 2020 May;38(2-03):168-178. doi: 10.1055/s-0040-1718741. Epub 2020 Oct 26.
Adenomyosis is a nonmalignant uterine disorder in which endometrial tissue exists within and grows into the myometrium. Animal models have generated limited insight into the still-unclear pathogenesis of adenomyosis, provided a platform for preclinical screening of many drugs and compounds with potential as therapeutics, and elucidated mechanisms underlying the pain and fertility issues that occur in many women with the disease. Spontaneous adenomyosis has been studied in nonhuman primates, primarily in the form of case reports. Adenomyosis is routinely experimentally induced in mice through methods such as neonatal tamoxifen exposure, pituitary engraftment, and human tissue xenotransplantation. Several studies have also reported hormonal or environmental toxicant exposures that give rise to murine adenomyosis, and genetically engineered models have been created that recapitulate the human-like condition, most notably involving alteration of β-catenin expression. This review describes the animal models for adenomyosis and their contributions to our understanding of the factors underpinning the development of symptoms. Animal models represent a unique opportunity for understanding the molecular basis of adenomyosis and developing efficacious treatment options for affected women. Herein, we assess their different potentials and limitations with regard to identification of new therapeutic interventions and reflect on future directions for research and drug validation.
子宫腺肌病是一种非恶性的子宫疾病,其中子宫内膜组织存在于并生长到子宫肌层中。动物模型为仍不清楚的子宫腺肌病发病机制提供了有限的认识,为许多具有治疗潜力的药物和化合物的临床前筛选提供了平台,并阐明了许多患有这种疾病的妇女出现疼痛和生育问题的机制。非人类灵长类动物中的自发性子宫腺肌病已被研究,主要是通过病例报告的形式。腺肌病通常通过新生期他莫昔芬暴露、垂体移植和人组织异种移植等方法在小鼠中进行实验诱导。一些研究还报告了激素或环境毒物暴露会导致小鼠发生子宫腺肌病,并且已经创建了基因工程模型来重现人类样的情况,其中最引人注目的是涉及β-连环蛋白表达的改变。这篇综述描述了子宫腺肌病的动物模型及其对我们理解导致症状发展的因素的贡献。动物模型为我们理解子宫腺肌病的分子基础和为受影响的女性开发有效治疗方案提供了独特的机会。在此,我们评估了它们在识别新的治疗干预措施方面的不同潜力和局限性,并反思了未来的研究和药物验证方向。