SPERMATOGENIC CELLS ON DEFINED SUBSTRATES FOR TOXICOLOGY

THE GOAL OF OUR PHASE I RESEARCH PROGRAM IS TO ESTABLISH CULTURE CONDITIONS THAT WILL MAINTAIN DIFFERENTIATED CELL FUNCTIONS IN RAT SERTOLI CELL-SPERMATOGENIC CELL CO-CULTURES FOR EXTENDED TIMES, USING DEFINED SUBSTRATES, AND SERUM-FREE MEDIUM, AND FUNCTIONAL ASSAYS. THE CULTURES WILL BE EVALUATED FOR SUITABILITY FOR TOXICOLOGICAL TESTING AND REPRODUCTIVE HORMONE ASSAYS USING AS MODEL TOXICANTS CHEMOTHERAPEUTIC DRUGS WITH KNOWN TESTICULAR TOXICITY. THE DEFINED SUBSTRATES WILL BE BASED ON COLLAGEN-GLYCOSAMINOGLYCAN CROSSLINKED COPOLYMERS. BOTH INCREASED LONGEVITY AND ADDITIONAL STAGES OF DIFFERENTIATION ARE IMPORTANT OBJECTIVES FOR TOXICOLOGICAL ASSAYS BECAUSE THEY ALLOW FOR BETTER STANDARDIZATION OF CULTURES, LONGER CONTACT TIMES FOR AGENTS TO BE TESTED, IDENTIFICATION OF PARTICULARLY SENSITIVE SPERMATOGENIC CELL TYPES AND DIFFERENTIATION SUBSTAGES, AND GREATER SENSITIVITY AND RANGE IN OBSERVING TOXIC ENDPOINTS. OUR DATA MAY ALSO BE OF CLINICAL SIGNIFICANCE SINCE SHORT TERM ASSAYS OF EFFECTS OF CHEMOTHERAPEUTIC DRUGS ON SPERMATOGENIC CELL DIFFERENTIATION MAY BE USEFUL IN PREDICTING THE POTENTIAL OF CHEMICAL-INDUCED STERILITY IN CANCER PATIENTS OF REPRODUCTIVE AGE. THE USE OF DRUGS WITH LOWER TOXICITY TO TESTICULAR CELLS MAY THEN BE CONSIDERED IN THESE PATIENTS. KNOWLEDGE GAINED FROM OUR WORK MAY ALSO HAVE VALUE IN THE UNDERSTANDING AND TREATMENT OF HUMAN INFERTILITY.