title: Effects of supplemental L-methionine on E-64 [trans-epoxysuccinyl-1-leucyl-amido (4-guanido) butane]-induced dysmorphology in rat embryos cultured in vitro.
abstract: E-64 [trans-epoxysuccinyl-1-leucyl-amido (4-guanido) butane] is teratogenic, inducing a spec-trum of malformations in vivo and producing similar effects in vitro. Numerous studies support the concept that E-64-induced malformations result from embryonic nutritionaldeficiency, without affecting the maternal nutritional status. This has provided a useful model with which to investigate the nutritional requirements of the early embryo, as well as the role of various nutrients in the etiology of congenital defects. In the current investigation, we examined effects of L-methionine on E-64-induced embryotoxicity in vitro. For these experiments, we cultured rat embryos 9.5 days postconception (p.c.) for 48 hours with E-64 and/or L-methionine. We found that the addition of L-methionine to E-64-exposed cultures reduced optic abnormality and increased embryo protein. These results suggest that embryopathy largely results from a deficiency of L-methionine although E-64 limits the supply of all amino acids to the embryo. Furthermore, although endocytosis and degradation of proteins by the visceral yolk sac (VYS) supply most amino acids to the embryo, free amino acids may be compensatory when this source is reduced. These results support those of previous investigations that suggest L-methionine is a limiting nutrient for embryonic development.
authors.affiliation: Department of Pediatrics, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan. tokino@m2.kufm.kagoshima-u.ac.jp
authors.forename: Kouichi
authors.initials: K
authors.lastname: Yoshidome
authors.forename: Hidehiko
authors.initials: H
authors.lastname: Kobae
authors.forename: Kimie
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Kiyoko
authors.initials: K
authors.lastname: Sameshima
authors.forename: Koichiro
authors.initials: K
authors.lastname: Miyata
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Kawano
mesh_terms: D000014:Abnormalities, Drug-Induced / Q000517:prevention & control*; D000818:Animals; D046508:Culture Techniques; D005314:Embryonic and Fetal Development / Q000187:drug effects*; D005260:Female; D007930:Leucine / Q000031:analogs & derivatives* / Q000633:toxicity*; D008297:Male; D008715:Methionine / Q000008:administration & dosage* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013723:Teratogens / Q000633:toxicity*
chemical_list: D013723:Teratogens; D008715:Methionine; D007930:Leucine; C024974:E 64