Project Grant R15DC020315

THE EFFECTS OF LIFE-LONG EXPOSURE TO LOW DOSES OF BISPHENOL A ON THE DEVELOPMENT AND USE OF VOCAL PATHWAYS IN X. LAEVIS - PROJECT SUMMARY ENDOCRINE DISRUPTING CHEMICALS (EDCS) ARE KNOWN HAZARDS WHICH ARE STILL PREVALENT IN THE ENVIRONMENT AND IN THE HUMAN HOME. BISPHENOL A (BPA) IS A KNOWN EDC FOUND IN COMMON ITEMS FROM PLASTIC TO PAPER RECEIPTS. RECENT EVIDENCE SUGGESTS THAT BPA IS PRESENT IN AMERICANS AT LEVELS HIGH ENOUGH TO CAUSE DETRIMENTAL EFFECTS ON LANGUAGE ACQUISITION IN MALE, HUMAN CHILDREN. THOUGH SUCH LEVELS ARE CONSIDERED SAFE FOR ACUTE, ADULT EXPOSURE, THE IMPACT OF LONG-TERM, LOW-DOSE EXPOSURE TO EDCS DURING DEVELOPMENT IS AN UNDERSTUDIED PHENOMENON WITH POTENTIALLY SERIOUS IMPACTS ON HUMAN HEALTH. THE AIMS OF THIS STUDY ARE TO: 1) TO TRACK THE IMPACT OF LOW-DOSE BPA EXPOSURE ACROSS DEVELOPMENT INTO ADULTHOOD, AND 2) TO IDENTIFY THE MECHANISMS UNDERLYING VOCAL DEFICITS CAUSED BY ENDOCRINE DISRUPTION. THE PROPOSED STUDIES INCLUDE IN VIVO ANALYSES OF JUVENILE DEVELOPMENT AND BEHAVIOR AS THEY TRANSITION INTO ADULT VOCAL BEHAVIOR PATTERNS. THE IN VIVO WORK IS COMPLEMENTED WITH IN VITRO ANALYSIS OF THE LARYNX AND THE NEURAL STRUCTURES WITHIN THE BRAIN THAT DRIVE VOCALIZATION. THESE STUDIES UTILIZE THE SOUTH AFRICAN CLAWED FROG, XENOPUS LAEVIS, AS A MODEL ORGANISM. THE MECHANISMS DRIVING X. LAEVIS VOCALIZATION PATTERNS ARE WELL-STUDIED, AND THEIR VOCAL BEHAVIORS ARE VARIED BUT NOT COMPLEX. X. LAEVIS PRODUCE AT LEAST SEVEN DIFFERENT TYPES OF VOCALIZATION; SOME ARE MALE-SPECIFIC, SOME ARE FEMALE-SPECIFIC, AND ALL ARE USED IN SPECIFIC SOCIAL CONTEXTS. THE VARIATION IS VOCAL PATTERNS IS BALANCED BY THE FACT THAT THE CALLS ARE INNATE AND DO NOT NEED TO BE LEARNED. XENOPUS VOCAL BEHAVIOR IS EASILY QUANTIFIED. CALLS HAVE DISTINCT FEATURES WHICH MAKE THEM EASILY COUNTED AS DISTINCT UNITS. EACH CALL IS ALSO COMPOSED OF SOUNDS THAT HAVE DISTINCT TEMPORAL AND SPECTRAL FEATURES WHICH CAN ALSO BE QUANTIFIED FOR COMPARISONS. THE TEMPORAL AND SPECTRAL COMPONENTS OF VOCALIZATIONS ARE GENERATED BY THE VOCAL PATTERN GENERATOR IN THE BRAIN AND THE RESONANCE STRUCTURES WITHIN THE LARYNX (RESPECTIVELY,) AND BOTH STRUCTURES HAVE ROBUST IN VITRO PREPARATIONS THAT ALLOW FOR MECHANISTIC STUDY. THUS, THE X. LAEVIS VOCAL SYSTEM IS WELL SUITED FOR STUDIES OF LANGUAGE DISRUPTION BY EDCS LIKE BPA, BECAUSE ABERRATIONS ARE EASILY IDENTIFIED AND PROXIMAL CAUSES CAN BE DIRECTLY INVESTIGATED. THIS INVESTIGATION WILL PROVIDE INSIGHT HOW BPA IMPACTS LANGUAGE DEVELOPMENT, ALLOWING US TO IDENTIFY POTENTIAL TARGETS FOR SPEECH THERAPY AS WELL AS HIGHLIGHTING THE POTENTIAL HAZARDS OF LONG-TERM, LOW-DOSE EXPOSURE TO EDCS.