EMBRYOTOXICITY OF CARBAMAZEPINE IN RAT POSTIMPLANTATION EMBRYO CULTURE AFTER IN-VITRO EXPOSURE VIA 3 DIFFERENT ROUTES

Postimplantation rat embryo culture is used widely for studies of embr yotoxic effects on the isolated embryo after in vitro exposure to xeno biotic compounds, In this study, the relevance of three routes of expo sure of the embryo in vitro was evaluated using the embryotoxic antico nvulsant carbamazepine. Embryotoxic effects were assessed, and analyse s in conceptus tissues were done to reveal uptake and metabolism of th e compound, Exposure via the culture medium resulted in neural tube de fects and general retardation of growth and development, After injecti ons into the amniotic or exocoelomic space, local membrane adhesions w ere found. Intra-amniotic exposure caused adhesions of the amniotic me mbrane with the embryonic neural plate, resulting in trapping of the m embrane in the closing neural tube, as well as in open neural tube def ects occurring in various areas of the neural tube, Only after exposur e via the culture medium were amounts of carbamazepine detectable in t he embryonic tissue, correlating with the systemic effects found, It i s concluded that uptake from the culture medium via the yolk sec circu lation is the relevant exposure route to be used for embryotoxicity ef fect assessment, (C) 1998 Elsevier Science Inc.