Tuesday, 24 May 2005

This presentation is part of: ADMET Posters

Essential Fatty Acid Metabolizing Enzymes Expression in the Developing Rat Placenta and Trophoblastic Models

Yan Xu, Gregory T. Knipp, and Thomas J. Cook. Rutgers, the State University of New Jersey, Piscataway, NJ

The placenta regulates the delivery of nutrients and xenobiotics to the fetus, thus nourishing and protecting the fetus during development. Metabolism and transport are the two primary processes that govern essential fatty acids (EFA) supply from mother to fetus, which are critical for fetal development. While the EFA metabolism pathways are described in many tissues, there is a dearth of information in placenta. In this study, we have determined the expression of several enzymes involved in EFA metabolism in the rat developing placenta and trophoblastic models: cytochrome P450 isoforms CYP4A1, 4A2, 4A3, and 4A8; cyclooxygenases COX-1 and 2; lipoxygenases 12/15- and 5-LOX. Placentas from rats on different gestation period were harvested. The junctional (JXN) and labyrinth (LAB) zones were separated. HRP-1 and Rcho-1 trophoblstic models were cultured. Gene expression was determined by RT-PCR using specific primers. Immunohistochemistry was utilized to determine the temporal and spatial protein expression. The relative expression of the CYP4As were: 4A1>4A2>4A3, 4A8, with greater expression in the JXN zone. COX-2 exhibited a greater expression than COX-1 after gestational day 11 with a shift in spatial expression from LAB to JXN as gestation progressed. 12/15-LOX was expressed throughout the gestation with 5-LOX undetected. The results demonstrate that the rat placenta expresses several enzymes involved in EFA metabolism. The differential expression suggests that there may be changes in placental EFA metabolism as a function of gestational age that can alter EFA supply to the fetus. Our work establishes a template for studying xenobiotics influence on placental EFA metabolism.

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