Morphologic characteristics of endometriosis in the mouse model: application to toxicology

Surgically induced endometriosis in the mouse has been described as a model to investigate the effect of environmental pollutants on the growth of endometriotic implants. The objectives of this study were to evaluate a modified surgical procedure to induce endometriosis and validate the model by comparing the effects of estrogen, 4-chlorodiphenyl ether (4-CDE) as a possible estrogenic contaminant, and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a contaminant with predominantly anti-estrogenic activities, on the growth of endometrial implants. Uterine strips (1.0 x 4.0 mm2) were autotransplanted to multiple sites in the abdomen of sexually mature female B6C3F1 mice (n = 33), which were randomly assigned to the following groups: intact control (n = 4); ovariectomized (OVX, n = 9); OVX and treated with 4-CDE (n = 6); OVX and treated with 17 beta-estradiol (E2, n = 9); and OVX and treated with E2 plus TCDD (n = 5). Endometrial implants survived warm ischemia regardless of implant site and appeared as small clear spherical or ovoid fluid-filled cysts. The diameter of the endometrial cysts in the OVX animals was significantly (p < 0.0001) smaller compared with the intact animals and OVX animals replaced with E2 or 4-CDE. In contrast, TCDD treatment inhibited the growth of endometrial cysts in the presence of estrogen. We conclude that autotransplantation of uterine slices to multiple abdominal sites results in formation of endometriotic cysts that are responsive to estrogen, and that environmental contaminants possess the potential to affect the survival and growth of endometrial cysts. Therefore, we concluded that the mouse endometriosis model described in this paper has applications to investigate the possible role of environmental pollutants in the development of endometriosis.