Adenomyosis - A result of disordered stromal differentiation

Adenomyosis is a fairly frequent disorder in adult women characterized by t he haphazard location of endometrial glands and stroma deep within the myom etrium of the uterus. This study compared the effects on uterine developmen t of the selective estrogen receptor modulators, tamoxifen, toremifene, and raloxifene with estradiol when given orally to female mice on days 2 to 5 after birth. Uterine adenomyosis was found in all (14 of 14) mice dosed wit h tamoxifen and most mice (12 of 14) treated with toremifene, but in none o f the vehicle-dosed controls, in only one animal treated with raloxifene at 42 and 90 days after dosing and in none of the mice treated with estradiol at 42 days. At 6 days, the uterus in the groups that developed a high inci dence of adenomyosis showed histological evidence of disturbed differentiat ion of the myometrium. Gene-expression XY-scatterplots using Clontech mouse 1.2 Atlas mouse cDNA expression arrays analyzing total uterine RNA showed nerve growth factor-alpha, preadipocyte factor-1, and insulinlike growth fa ctor-2 were key genes differentially modified by tamoxifen or toremifene tr eatment, relative to the controls. As these genes may play an important rol e in regulating differentiation and development of the myometrium, these da ta suggest that adenomyosis may be caused primarily by defects in the forma tion of the myometrium.