The pathogenesis of uterine adenomyosis

The exact aetiology and pathogenesis of uterine adenomyosis are not clear. Increased endometrial invasiveness has been proposed in the literature, but without conclusive evidence. This thesis was undertaken to examine the pathogenesis of adenomyosis and the differences between affected and unaffected uteri, testing two possibilities with adenomyosis: (i) that the myometrium is permissive to invasion by a normal basal endometrium, or (ii) that the basal endometrium has a higher invasive potential and penetrates a normal myometrium. To examine the early phases of development of adenomyosis, a mouse model was used, where adenomyosis was induced by dosing female pups with tamoxifen. The same experiment was used on C57/BL6J strain to examine strain differences in response to tamoxifen and predisposition to adenomyosis. Adenomyosis in the human uterus was characterised, examining the immunohistochemical, light and electron microscopy structure, and RNA microarrays of affected and unaffected uteri. The invasive properties of the stroma and its interaction with the underlying myometrium were further studied in a co-culture model. Adenomyosis was successfully induced in the CD1 mice, with abnormal development and disruption ... (continues)