Stimulating effects of 4-chlorodiphenyl ether on surgically induced endometriosis in the mouse

The objectives of this study were to evaluate the effects of repeated injection of 4-chlorodiphenyl ether (4-CDE) on the survival and growth of endometriotic implants. Endometriosis was surgically induced in adult female B6C3F1 mice (n = 25) after ovariectomy. Seven days later the animals were randomly divided into five groups and treated with vehicle alone (corn oil, control), or 20 micrograms/kg/d estrone (positive control), or 10, 75, or 150 mg/kg/d 4-CDE in vehicle for 28 d. The number and size of the endometriotic cysts were recorded and the cysts were then harvested for histology at necropsy 2 d after the last treatment. There were significantly more cysts formed (P < 0.05) in the 150 mg/kg/d 4-CDE group compared to the vehicle-treated control (60 vs. 8%), but not compared to the estrone-treated positive control (90 vs. 60%). Hepatic enzymes were evaluated to confirm exposure and to further clarify the enzymatic route of 4-CDE biotransformation by the liver. In conclusion, the repeated exposure to 4-CDE increased the survival rates of the endometriotic cysts in the ovariectomized mouse, which suggests that 4-CDE mimics estrogen effects on endometriotic tissues because the endometrial tissues are dependent on estrogenic support for survival.