In the past, most studies dealing with the nutrition of the conceptus have been performed in the early or late stages of fetal development. A number of developments permit us to perform nutritional studies during the earliest period of organogenesis. These developments include the preparation of standardized embryotoxic and teratogenic antibodies, the development of rodent embryo culture methods and the quantitation of endocytosis into a reproducible methodology. Furthermore, the unique placentation in the rodent permits one to combine the above methodologies into experiments which can define several parameters of early embryonic nutrition, as well as determine the changing roles of the yolk sac and chorioplacenta throughout gestation.
The specific aims of this program are (1) to study placental (yolk sac and chorioplacental) transport of small molecules and macromolecules (endocytosis) from early organogenesis to late gestation in normal and pathologic states utilizing in vitro (embryo culture, yolk sac culture) and in vivo techniques; 2) to study the two sources of amino acids for rat embryonic development, histiotrophic nutrition (intracellular digestion of exogenous proteins) versus the transport of exogenous free amino acids in the presence or absence of teratogenic antiserum; 3) to obtain endocytosis-reducing antibodies and/or teratogenic antibodies uncontaminated with non-specific gamma globulin by utilizing the monoclonal antibody technique; 4) to study the effect of antiserum prepared against primate yolk sac on primate development. These studies should permit the quantitation of the parameters of early embryonic nutrition and the evaluation of the role of placental dysfunction in embryopathology, as well as a reevaluation of the role of the yolk sac in early primate development. Furthermore, teratogenic antibodies provide a unique and important tool to study embryonic nutrition in the mammal during organogenesis and early fetal development. The uniqueness and importance of this research is related to several features: (1) the impact of protein and amino acid deprivation on the developing embryo can be studied both in vivo and in vitro; (2) the effect of malnutrition on the embryo can be studied without interfering with maternal nutrition; (3) these studies have clinical relevance because yolk sac dysfunction may be a contributing factor to human teratogenesis; and (4) quantifying yolk sac dysfunction which precedes teratogenesis may give us insight into the prevention of congenital malformations by either nutritional or pharmacological methods.
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