Evaluation of various toxicants in rabbit whole-embryo culture using a newmorphologically-based evaluation system

In an effort to advance the use of whole-embryo culture (WEC) techniques in the rabbit, we recently developed a gestational-age-based quantitative mor phologic evaluation system for rabbit embryos. In the current study, we app lied this new morphological scoring system to assess the development of rab bit gestational day (gd) 9 embryos exposed for 48 hr in WEC to the teratoge ns ethanol (EtOH, 154 mM), 6-aminonicotinamide (6AN, 0.15 mM), and methoxya cetic acid (MAA, 5.0 mM), and the nonteratogen penicillin G (PG, 2.0 mM). E ach teratogen at the concentration tested markedly inhibited morphological development, as indicated by significantly lower morphologic scores (10.1 /- 0.05, EtOH; 10.2 +/- 0.05, 6AN; and 9.8, MAA) relative to controls (10.6 +/- 0.04), and resulted in an increased percentage of malformed embryos (5 3%, EtOH; 57%, 6AN; 90%, MAA; and 3%, control). Embryonic growth, as measur ed by head length, somite number, and total embryonic protein, was signific antly decreased by each teratogen. The abnormalities produced by teratogen exposure, which included brain, somite, and facial defects, were often simi lar to those produced following in vivo exposure in rabbits and rodents, an d/or in vitro exposure in rodents. In contrast to the teratogen exposure gr oups, PG had no effect on embryo growth parameters, or on malformation rate (6%), although a slight but statistically significant decrease in morpholo gy score (10.5 +/- 0.03) was noted. Our preliminary studies demonstrate the usefulness of the morphology evaluation system by quantifying graded diffe rences in development, and indicate that rabbit WEC may be a useful adjunct to rodent WEC in gaining insights regarding differential interspecies sens itivity. Teratology 59:102-109, 1999. (C) 1999 Wiley-Liss, Inc.