Animal Models of Adenomyosis

Abstract

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.

Figure 1.

The role of aberrant β-catenin activation in EMT and adenomyosis. (A) Representative immunostaining images showing the levels of β-catenin (a-c), E-cadherin (d-f), COUP-TFII (g-i), and E-cadherin/vimentin (red/green; j-l) in endometrium from control women (a, d, g, and j) and eutopic endometrium (b, e, h, and k) and adenomyosis lesions (c, f, i, and l) from women with adenomyosis. (B) Representative immunostaining images showing the levels of β-catenin (a-c), E-cadherin (d-f), COUP-TFII (g-i), and E-cadherin/vimentin (red/green; j-l) in endometrium from control mice (a, d, g, and j) and eutopic endometrium (b, e, h, and k) and adenomyosis lesions (c, f, i, and l) from mice with β-catenin activation (Pgr^cre/+Ctnnb1^f(ex3)/+).