The long term objective is to reduce the incidence of human reproductive failures through the identification of previously unknown or unsuspected reproductive toxins and through an understanding of the mechanisms by which they interfere with developmental processes. Based on previous studies in this lab and the work of others we propose to study one possible cause of reproductive failure involving the following sequence: (I) pollutants act on basement membranes in the maternal organism causing the release of the membrane specific protein laminin, (II) anti-laminin antibodies are produced and infiltrate the lumen of the uterus and (III) early embryos fail to develop because anti-laminin antibodies block the uptake and/or utilization of nutrient proteins by the endodermal cells of visceral yolk-sac. Studies are proposed using rats as well as monkeys to demonstrate that pollutants can cause the production of anti-laminin antibodies which appear in the uterine lumen and that the presence of these antibodies can be associated with reproductive failures. Additional studies with in vitro cultures of whole rat embryos are designed to identify the immunological mechanism for the embryo toxicity of anti-laminin antibody and the specific visceral yolk-sac endodermal cell function(s) blocked by the antibody. Finally, attempts will be made to overcome the embryo-toxicity of anti-laminin antibody in the intact animal by providing specifically those nutrients that were found to overcome embryo toxicity in the in vitro whole embryo culture studies.
Showing the most recent 10 out of 14 publications
