Promotion of endometriosis by 2,3,7,8-tetrachlorodibenzo-p-dioxin in rats and mice: time-dose dependence and species comparison.
In the disease of endometriosis, endometrial tissue grows outside the uterus, usually in the peritoneal cavity. Rodent models of endometriosis allow a way to reproduce the disease, evaluate effects of chemicals, and study mechanisms. Twenty-one days prior to induction surgery which 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 micrograms TCDD/kg. Animals were treated again at the time of surgery 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 increase in endometriotic site diameter when all time points were pooled within each dose in rats and a dramatic increase in site diameter in mice at 9 and 12 weeks. In rats but not mice, ovarian weight was decreased 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 antrophy, indicating immune dysfunction, and hepatomegaly were observed as consequences of TCDD exposure. Body weight was reduced in rats but not in mice. Histological evaluations of endometriotic sites revealed fibrosis in control rats, necrotic and inflammatory changes in the sites from 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 diameter (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 TCDD suggest that the mechanisms mediating TCDD's action to promote endometriosis 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.
Cummings
A M
AM
Developmental Toxicology Division, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA.
Metcalf
J L
JL
Birnbaum
L
L
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004715:Endometriosis / Q000139:chemically induced* / Q000473:pathology; D004971:Estrus / Q000187:drug effects; D005260:Female; D008099:Liver / Q000187:drug effects; D051379:Mice; D009929:Organ Size / Q000187:drug effects; D010053:Ovary / Q000187:drug effects / Q000473:pathology; D000072317:Polychlorinated Dibenzodioxins / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013045:Species Specificity; D013950:Thymus Gland / Q000187:drug effects; D013997:Time Factors; D014599:Uterus / Q000187:drug effects
D000072317:Polychlorinated Dibenzodioxins