Effects of supplemental methionine on antiserum-induced dysmorphology in rat embryos cultured in vitro

Background: Heterologous antiserum to the visceral yolk sac (AVYS) is terat ogenic, inducing a spectrum of malformations in vivo and producing similar effects in vitro. Numerous studies support the concept that AVYS-induced ma lformations result from embryonic nutritional deficiency, without affecting the maternal nutritional status. This has provided a useful model with whi ch to investigate the nutritional requirements of the early embryo, as well as the role of various nutrients in the etiology of congenital defects. Methods: In the current investigation, we examined the effects of methionin e and other nutrients on AVYS-induced embryotoxicity in vitro. For these ex periments, we cultured rat embryos (9.5 p.c) for 48 hr with AVYS and/or met hionine at several concentration levels. Results: The addition of L-methionine to AVYS-exposed cultures reduced dysm orphology and open neural tube; this effect was concentration dependent. AV YS-induced dysmorphology was completely prevented at a concentration of L-m ethionine corresponding to 50-fold the basal serum concentration. Utilizati on of D-methionine, L-leucine, or folic acid (5-methyltetrahydrofolate, MTH F) instead of L-methionine had no protective effects. Conclusions: These results suggest that, although AVYS limits the supply of all amino acids to the embryo, embryopathy largely results from a deficien cy of methionine. Furthermore, although endocytosis and deg radation of pro teins by the VYS supplies most amino acids to the embryo, free amino acids may be compensatory when this source is reduced. These results support thos e of previous investigations that suggest methionine is required for normal NT closure and that methionine is a limiting nutrient for embryonic develo pment. (C) 2000 Wiley-Liss, Inc.