Significance Granulosa cells and oocytes obtained from suprovulated female cynomolgus macaques are used to evaluate the effects of potential reproductive toxins. Objectives Currently, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a highly toxic dioxin, is being evaluated in primate reproductive cells. Results We have found that TCDD modulates the function of the granulosa cells via the cyclic AMP signalling system and it reduces the glucose transporting activity. Also, TCDD decreases estrogen production but not aromatase activity in the granulosa cells. Recent results show that relaxin production is also altered by TCDD in human granulosa cells. Because TCDD appears to have similar effects in human and nonhuman primate luteinizing granulosa cells, we will continue our studies of the effects of TCDD on relaxin in the macaque cells as well as human. We plan to compare our results of in vitro TCDD treatment with the effects of TCDD in vivo. We are also utilizing the luteinizing granulosa cells as an in vitro model of corpus luteum function. We have recently found that the anti-progestin, RU486, leads to decreases in estrogen, progesterone and relaxin production by these cells without affecting cell number or viability. Future Directions We will continue experiments to elucidate the mechanisms for control of relaxin production. We also plan to utilize these cells to produce preliminary data on the study of mechanisms of luteolysis in vitro and to compare these results with in vivo studies. KEYWORDS dioxins, ovarian function, reproductive toxicology
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