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From the Medical Research Council Toxicology Unit, Leicester, United Kingdom
Adenomyosis is a fairly frequent disorder in adult women
characterized by the haphazard location of endometrial glands and
stroma deep within the myometrium of the uterus. This study compared
the effects on uterine development 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 with tamoxifen and most mice (12 of 14) treated with
toremifene, but in none of 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 incidence
of adenomyosis showed histological evidence of disturbed
differentiation 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-
, preadipocyte
factor-1, and insulin-like growth factor-2 were key genes
differentially modified by tamoxifen or toremifene treatment,
relative to the controls. As these genes may play an important role in
regulating differentiation and development of the myometrium,
these data suggest that adenomyosis may be caused primarily by defects
in the formation of the myometrium.
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  A. Hever, R.B. Roth, P.A. Hevezi, J. Lee, D. Willhite, E.C. White, E.M. Marin, R. Herrera, H.M. Acosta, A.J. Acosta, et al. Molecular characterization of human adenomyosis Mol. Hum. Reprod., December 1, 2006; 12(12): 737 - 748. [Abstract] [Full Text] [PDF]
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