Significance The working hypothesis in this study was that TCDD acts, in part, by activating Src-kinase, that a Src-kinase inhibitor, such as geldanamycin, could block the adverse effects of TCDD. Objectives Since TCDD causes early fetal loss (EFL) in the monkey model, then pre-treatment with geldanamycin should prevent TCDD-induced EFL as long as geldanamycin administration was maintained. Results A single oral dose of TCDD at 2 5g/kg BW on gestation day (GD) 13, along with 3 IM treatments of geldanamycin on GD's 12, 17 and 22 at 1.0 5g/kg BW was administered to a single pregnant female. Daily urine samples were collected prior to treatment through GD45, with blood collected from GD 7 to GD 44 at least once per 3 days. Bioactive and immunoreactive mCG were measured as a biomarker for the effects of TCDD on trophoblast development and/or function. Serial ultrasound exams throughout early pregnancy show normal fetal development until approximately GD48, with the subsequent exam on GD 62 showing fetal death with gestational age estimation measuring at approximately 58-59 days. The fetus was retained for approximately 4 months, whereby no mensing was detected. Mensing resumed approximately 45 days later. Future Directions Geldanamycin blocked all adverse effects of TCDD during its administration. If the results can be generalized then it would appear that blocking Src-kinase (or some other component of the AhR/Src/HSP complex) is essential for TCDD to exert its toxic effects on the products of conception in the primate model. KEY WORDS cynomolgus macaque, early fetal loss, geldanamycin, SrC-kinase, TCDD FUNDING NIH Grant RR00169
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