A study of the effect of experimentally-induced neural tube lesions on amniotic fluid concentrations of alpha-fetoprotein, albumin, alpha-2 macroglobulin and spinal fluid beta 2aT(trace)-protein will be performed using rat embryos. Neural tube defects will be induced by maternal feeding of vitamin A or by direct X-irradiation of embryos in utero or in embryo culture. Normal and abnormal embryos and fetuses will be obtained at regular intervals after teratogen exposure and the amniotic fluid concentrations of the proteins measured immunochemically. Normal and in utero-teratogen-exposed embryos will be grown in vitro. Net alpha-fetoprotein synthesis and radiolabeled amino acid incorporation into alpha-fetoprotein by normal and abnormal embryos will be measured. Embryos, in cultures initiated from days 8 to 10 of gestation, will be exposed briefly to the teratogens, and the critical time for in vitro induction of neural tube defects established. The transfer rates of albumin-I131 and alpha-fetoprotein-I125 from the amniotic fluid space to the fetal serum will be determined in normal and neural tube- defective fetuses. Albumin-I131 and alpha-fetoprotein-I125 half-life measurements will indicate if neural tube defects alter the catabolism of these proteins. The concentrations and ratios of alpha-fetoprotein concanavalin A-affinity molecular variants will be measured in each experimental system. These studies will elucidate the mechanism(s) by which amniotic fluid alpha-fetoprotein synthesis and metabolism are altered by neural tube defects, and they will reveal if the effect on alpha-fetoprotein is specific. The in vitro embryo culture system will provide a means to study alpha-fetoprotein metabolism quantitatively and to test suspected neural tube and other organ teratogens, independent of maternal influences which may explain the lack of response to certain teratogens exhibited by various species. BIBLIOGRAPHIC REFERENCES: Smith, C.J., Bisbee, W. B. and Kelleher, P.C., 1976. Effect of growth hormone on collagen metabolism of the rat. V International Congress of Endocrinology, Hamburg, Germany, July 18-24, 1976. Kelleher, P.C. and Bisbee, W.B., 1976. Excretion of glycosolated hydroxylysines by patients with metabolic bone disease. V International Congress of Endocrinology, Hamburg, Germany, July 18-24, 1976.
NIH ExPorter
NIH ExPorter