Jz. Yang et al., Subchronic exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin modulates the pathophysiology of endometriosis in the cynomolgus monkey, TOXICOL SCI, 56(2), 2000, pp. 374-381
An increase in the incidence and severity of endometriosis following treatm
ent with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was a serendipitous fin
ding in a reproductive toxicology study in rhesus monkeys, The purpose of t
his study was to investigate the effects of subchronic exposure to TCDD on
the survival and growth of surgically implanted endometrial fragments. Endo
metrial fragments of equal size (4 x 1 mm(2)) 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 tr
eatment in the early to mid luteal phase and the maximal and minimal endome
trial 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%, respect
ively). In contrast, exposure to 3.57 and 17.86 ng/kg/day TCDD for 1 year r
esulted 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 char
acteristics. It is concluded that TCDD facilitates the survival of endometr
ial implants and exerts a bimodal effect on endometrial implant growth.