Our studies focus on the biology of the growing chicken oocyte and the developing chicken embryo. Specifically, we are interested in unraveling molecular mechanisms involved in the transport of VLDL from the egg yolk to the embryo proper.

In this context, the roles of the LDL receptor gene family members, apolipoproteins and lipid transfer proteins are studied. The developing avian embryo constitutes an excellent system for the study of lipid and lipoprotein transport phenomena. The yolk is the major source of nutrients for the developing embryo, but molecular details of the delivery mechanisms are largely unknown. During the vitellogenic phase of ocyte growth in the chicken, the yolk accumulates via uptake from the circulation of precursor proteins, serves as the sole source of lipid, carbohydrate, and protein. Only 350 mg of the 5-6 g of lipid in the yolk are mobilized during the first two weeks of embryogenesis; the major portion is transported during the final week. Such uptake, to a large part, occurs via the yolk sac, which utilizes the yolk lipoprotein components, following their degradation or modification, for re-synthesis of lipoproteins which are subsequently secreted and delivered to the embryo through the embryonic circulatory system.

The chick yolk sac is characterized by an outer layer of loosely associated mesenchymal tissue containing fetal blood islands and an inner single layer of endodermal cells which line the lumen of the yolk sac cavity. The yolk-sac derived lipoproteins, mainly VLDL contain much higher proportions of cholesteryl esters than yolk VLDL and harbor the intact form of apoB-100 rather than proteolytic fragments thereof. Furthermore, they lack apoVLDL-II, which is synthesized by laying hens and is present in yolk VLDL. These findings suggest that processing of yolk components inside the yolk sac proceeds in controlled fashion, initially involving degradation of their constituents.

We also focus on the roll of LDL modification in atherogenesis. The onset of atherosclerosis is a complex process, but there is now some evidence that the modification of LDL may play a key role in early atherogenic events. Modifed LDL activates endothelial cells to attract and bind monocytes, and consecutively foam cells are formed, leading to the appearance of the fatty streak lesion. Various diseases such as diabetes, chronic renal insufficiency and obesity come along with elevated levels of blood cholesterol and different modified LDL. We are interested to identify compounds (synthetic, natural) with the potential to act as catalysts or inhibitors of the atherogenic modification of LDL.