Am. Cummings et al., PROMOTION OF ENDOMETRIOSIS BY 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN IN RATS AND MICE - TIME-DOSE DEPENDENCE AND SPECIES COMPARISON, Toxicology and applied pharmacology, 138(1), 1996, pp. 131-139
In the disease of endometriosis, endometrial tissue grows outside the
uterus, usually in the peritoneal cavity, Rodent models of endometrios
is allow a way to reproduce the disease, evaluate effects of chemicals
, and study mechanisms, Twenty-one days prior to induction surgery whi
ch produces endometriosis, female Sprague-Dawley rats and B6C3F1 mice
were pretreated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) at 0,
3 or 10 mu g TCDD/kg, Animals were treated again at the time of surger
y and at 3, 6, and 9 weeks following surgery. Evaluations were made at
3, 6, 9, and 12 weeks postsurgery. TCDD produced a dose-dependent inc
rease in endometriotic site diameter when all time points were pooled
within each dose in rats and a dramatic increase in site diameter in m
ice at 9 and 12 weeks. In rats but not mice, ovarian weight was decrea
sed at 9 and 12 weeks, the occurrence of persistent vaginal estrus was
increased at these times, and histological evaluation of the ovaries
revealed ovulatory arrest at 12 weeks. In both species, thymic atrophy
, indicating immune dysfunction, and hepatomegaly were observed as con
sequences of TCDD exposure. Body weight was reduced in rats but not in
mice. Histological evaluations of endometriotic sites revealed fibros
is in control rats, necrotic and inflammatory changes in the sites fro
m TCDD-treated rats, and predominantly fibrotic changes in sites from
TCDD-treated mice. Differences observed between the rat and the mouse
with respect to (a) the magnitude of the effect on endometrial site di
ameter (rats < mice), (b) measured effects on ovarian function (rats >
mice) that may be based on the partial antiestrogenicity of TCDD, and
(c) evidence that mice and rats differ in their immune response to TC
DD suggest that the mechanisms mediating TCDD's action to promote endo
metriosis are complex and may be different in rats and mice. The mouse
may be a better model for future studies necessary to elucidate these
mechanisms. (C) 1996 Academic Press, Inc.