Discovery of antibodies which apparently interfere with embryonic nutrition and the important finding that the majority of amino acids utilized for protein synthesis by the embryo during organogenesis stem from serum proteins degraded by the visceral yolk sac (VYS) rather than from free amino acids have focused our attention on aspects of fetal nutrition and the changing roles of the VYS and chorioallantoic placentae of the rat during gestation.
Our specific aims i n this proposal are: 1) to determine the in vivo fractional rates of total protein synthesis, net protein synthesis (growth) and protein degradation during organogenic and histogenic periods of gestation and the effect of teratogens, i.e., anti-rat VYS serum (AS), trypan blue (TB), and leupeptin (LP), on these parameters in the rat; 2) to determine the relative contribution of serum proteins versus serum free amino acids utilized for fetal protein synthesis in vivo during organogenic and histogenic periods of gestation and the effect of AS, TB and LP on these parameters; and 3) to determine relative net incorporation of amino acids stemming from serum proteins and serum free amino acids into fetal rat proteins which were supplied to the fetus via the chorioallantoic placenta versus the amino acids supplied via the VYS placenta in vitro and the effect of AS, TB, and LP on these parameters. Our studies will provide evidence, during a wide range of gestation, of changes in the kinetics of fetal protein metabolism, of changes in the relative importance of exogenous amino acids versus serum proteins as sources of amino acids, of changes in the relative magnitude of amino acid nutrition support of the fetus by the two placentae, and how fetal malnutrition resulting from placental dysfunction may play a primary role in teratogenesis induced by AS, TB, and LP.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD018167-06
Application #
3315163
Study Section
Human Embryology and Development Subcommittee 1 (HED)
Project Start
1984-04-01
Project End
1991-06-30
Budget Start
1990-07-01
Budget End
1991-06-30
Support Year
6
Fiscal Year
1990
Total Cost
Indirect Cost
Name
Thomas Jefferson University
Department
Type
Schools of Medicine
DUNS #
061197161
City
Philadelphia
State
PA
Country
United States
Zip Code
19107
Beckman, D A; Lloyd, J B; Brent, R L (1998) Quantitative studies on the mechanisms of amino acid supply to rat embryos during organogenesis. Reprod Toxicol 12:197-200
Beckman, D A (1997) Mechanisms of amino acid supply to the rat conceptus in normal and abnormal development. Reprod Toxicol 11:595-9
Beckman, D A; Solomon, H M; Buck, S J et al. (1994) Effects of dose and dose protraction on embryotoxicity of 14.1 MeV neutron irradiation in rats. Radiat Res 138:337-42
Brent, R L; Beckman, D A (1994) The contribution of environmental teratogens to embryonic and fetal loss. Clin Obstet Gynecol 37:646-70
Brent, R L; Beckman, D A; Landel, C P (1993) Clinical teratology. Curr Opin Pediatr 5:201-11
Beckman, D A; Pugarelli, J E; Koszalka, T R et al. (1991) Sources of amino acids for protein synthesis during early organogenesis in the rat. 2. Exchange with amino acid and protein pools in embryo and yolk sac. Placenta 12:37-46
Beckman, D A; Ornoy, A; Jensen, M et al. (1991) Ultrastructure and function of the rat yolk sac: damage caused by teratogenic anti-VYS serum and recovery. Teratology 44:181-92
Brent, R L; Beckman, D A (1990) Environmental teratogens. Bull N Y Acad Med 66:123-63
Beckman, D A; Pugarelli, J E; Jensen, M et al. (1990) Sources of amino acids for protein synthesis during early organogenesis in the rat. I. Relative contributions of free amino acids and of proteins. Placenta 11:109-21
Beckman, D A; Brent, R L (1990) Teratogenesis: alcohol, angiotensin-converting-enzyme inhibitors, and cocaine. Curr Opin Obstet Gynecol 2:236-45

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