DEVELOPMENTAL TOXICITY INDUCED DURING EARLY STAGES OF MAMMALIAN EMBRYOGENESIS

Both a conceptual and a practical borderland between teratology and mu tagenesis is early embryogenesis, the period between fertilization and gastrulation. Radiation and a variety of chemicals adversely affect t he early conceptus leading to in utero mortality and malformations. Th e post-fertilization period of susceptibility differs from exposures o f gametes, the later producing excessive pre-and peri-implantational d eath and low rates of fetal anomalies predominated by growth retardati on. In contrast mutagen exposure of the zygote induces peri-implantion al death, pan-gestational death and fetal anomalies predominated by hy drops, abdominal wall defects, and eye aberrations. The mechanism for this pathology remains unclear, These same agents produce a broader ra nge of phenotypic anomalies during the remainder of pre-gastrulation d evelopment with anomalies overlapping those induced during organogenes is. Retinoic acid and 5-azacytidine administered prior to gastrulation produce novel malformation syndromes indicative of gene expression mo dification. The rates and types of defects from mutagen treatment of b oth gametes and the early conceptus contrast with those resulting from embryonic treatment during organogenesis, and the mechanisms are like ly to differ. The pre-gastrulation period has not been explored to the extent reported during gametogenesis or organogenesis, Pre-gastrulati on teratology is a new area of investigation with relevance both to re productive toxicology and to mammalian developmental biology. (C) 1997 Elsevier Science B.V.