Effect of TCDD on Maternal Toxicity and Chorionic Gonadotropin——Bioactivity in the Immediate Post-implantation Period of Macaque

The pupose of this experiment was to observe the alterations in bioactivity of chorionic gonadotropin(CG) associated with early fetal loss(EFL).induced by the environmental toxin TCDD(1,3,7,8-tetrachlorodibenzo-p-dioxin) in the cynomolgus macaque.Ten of twelve females administered single doses of 1,2,or 4ug/kg TCDD on gestational day(GD) 12 had EFL from ten to twenty days later,Seven control animals treated only with the vehicle had normal pregnancies,Blood samples were repeatedly collected for hormone evaluation,from two days befor treatment to thirty-one days following treatment.Immunoreasctive monkey chorionic gonadotropin(mCG) was measured in serum using ELISA,and bioactive mCG was measured using a luminescence LH/CG bioassay.No change in immunoreactive mCG levels was detected as a result of TCDD,treatment,but bioactive mCG levels were significantly lower in TCDD-treated animals compared to controls.This change in bioactivity of mCG was also reflected in the ratio of mCG bioactivity to mCG immunoreactivity(B/I ratio) which began to rise in normal pregnancies by GD20,but did not rise in TCDD treated animals,These results demonstrate that normal pregnancy in the monkey,as in humans,is characterized by a post-implantation change in the B/I ratio of CG.These findings therefore suggest that changes in the production of bioactive CG may be used as a biomarker of environmental toxicant exposures which lead to EFL.

Effect of TCDD on maternal toxicity and chorionic gonadotropin--bioactivity in the immediate post-implantation period of macaque

The purpose of this experiment was to observe the alterations in bioactivity of chorionic gonadotropin (CG) associated with early fetal loss (EFL), induced by the environmental toxin TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) in the cynomolgus macaque. Ten of twelve females administered single doses of 1, 2 or 4 microg/kg TCDD on gestational day (GD) 12 had EFL from ten to twenty days later. Seven control animals treated only with the vehicle had normal pregnancies. Blood samples were repeatedly collected for hormone evaluation, from two days before treatment to thirty-one days following treatment. Immunoreactive monkey chorionic gonadotropin (mCG) was measured in serum using ELISA, and bioactive mCG was measured using a luminescence LH/CG bioassay. No change in immunoreactive mCG levels was detected as a result of TCDD, treatment, but bioactive mCG levels were significantly lower in TCDD-treated animals compared to controls. This change in bioactivity of mCG was also reflected in the ratio of mCG bioactivity to mCG immunoreactivity (B/I ratio) which began to rise in normal pregnancies by GD 20, but did not rise in TCDD treated animals. These results demonstrate that normal pregnancy in the monkey, as in humans, is characterized by a post-implantation change in the B/I ratio of CG. These findings therefore suggest that changes in the production of bioactive CG may be used as a biomarker of environmental toxicant exposures which lead to EFL.