Subchronic exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin modulates the pathophysiology of endometriosis in the cynomolgus monkey

Abstract

An increase in the incidence and severity of endometriosis following treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was a serendipitous finding in a reproductive toxicology study in rhesus monkeys. The purpose of this study was to investigate the effects of subchronic exposure to TCDD on the survival and growth of surgically implanted endometrial fragments. Endometrial fragments of equal size (4 x 1 mm2) were auto-transplanted to the pelvic cavity of nulliparous cynomolgus monkeys (Macaca fascicularis, n = 23), who were divided into 4 treatment groups and dosed 5 days a week with gelatin capsules containing 0, 1, 5, or 25 ng/kg body weight of TCDD mixed with glucose. Endometrial implant survival was monitored by laparoscopy at intervals of 1, 3, and 6 months. Animals were euthanized at 12 months of treatment in the early to mid luteal phase and the maximal and minimal endometrial implant diameter was measured. Both the maximal and minimal diameters were significantly reduced in the 0.71-ng/kg/day-TCDD dose group, compared to controls, whereas the survival rate was unaffected (20 vs. 16%, respectively). In contrast, exposure to 3.57 and 17.86 ng]kg]day TCDD for 1 year resulted in a significantly higher survival rate of implants (26.7% and 33.3% respectively vs. 16.0%) and significantly larger diameter implants in the 17.86-ng/kg/day dose group only, compared to the control group. Treatment had no effect on circulating gonadal steroid levels or menstrual cycle characteristics. It is concluded that TCDD facilitates the survival of endometrial implants and exerts a bimodal effect on endometrial implant growth.