SERINE-ENHANCED RESTORATION OF 2-METHOXYETHANOL-INDUCED DYSMORPHOGENESIS IN THE RAT EMBRYO AND NEAR-TERM FETUS

Effects of serine on restorative growth were characterized by comparin g embryo/fetal responses after maternal exposure to 2-methoxyethanol ( ME) and ME + serine by gavage on gestation day (gd) 13, a day of heigh tened limb sensitivity. Paws (gd 20) and limb buds (gd 15) were examin ed after ME alone at 50, 100, and 250 mg/kg, and after ME (either 100 or 250 mg ME/kg) + serine (1734 mg serine/kg) administered within minu tes (0 hr) to 24 hr after ME. Paw development was not altered after ME at 100 mg/kg, but was highly sensitive to 250 mg ME/kg with all fetus es and litters exhibiting defects (ectrodactyly, syndactyly, and short digit) in the preaxial region. In contrast, the limb bud displayed do se-related incidences of abnormalities after maternal treatment with t he low and high levels of ME. The condensing (precartilaginous, pentad actyl pattern) and noncondensing (undifferentiated mesenchymal cells) regions exhibited changes in their size, number, and location. Serine administration after 250 mg ME/kg was effective in reducing the occurr ence of paw dysmorphogenesis with its protection potency inversely rel ated to its delay of administration (i.e., 0% paw defect incidence aft er 0-hr delay, 25% after 4-hr delay, 41-45% after 8- and 12-hr delays, and 76% after 24-hr delay). The occurrences of limb bud pattern distu rbances produced by ME were also markedly decreased by serine cotreatm ent. Higher incidences of embryonic defects versus those of fetal defe cts demonstrate that restorative growth followed ME exposure. Serine a ttenuation of ME teratogenicity appears to emanate from enhanced resto rative growth so that tissue damage, which otherwise would be expresse d as a defect at parturition, is repaired and replaced to resume devel opment of the limb toward its normal structure. (C) 1997 Academic Pres s.