Identifying the ABCs of xenobiotic metabolism in protecting the germ line lineage

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PROJECT SUMMARY/ABSTRACT This project explores the cellular protection systems available to the primordial germ line—the embryonic precursors to egg and sperm. The research is centered on the developmental and protective functions of a class of multi-drug resistance ABC transporters that actively efflux toxins, reactive metabolites, and signaling molecules from the cell. It will use two model systems—the sea urchin embryo and a human cell line—to identify these functions in the development and protection of primordial germ cells (PGCs). PGCs have not been characterized in this context before, despite the ubiquitous presence of “low-dose” pollutants and drugs in the environment, umbilical cord blood and maternal fluids. Modeling the threshold of protective mechanisms in PGCs is crucial for predicting and mitigating early life exposures, in order to help define safe dosage levels and mitigate infertility issues that may arise in utero.