SPACE TRAVEL RESULTS IN ADAPTATION TO UNIQUE CONDITIONS THAT INCLUDE EXPOSURE TO LOW DOSES OF COSMIC RADIATION AND MICROGRAVITY AND HEIGHTENED STRESS. ADAPTING TO THESE PHYSIOLOGICAL AND PSYCHOLOGICAL STRESSORS CAN ALTER HORMONE AND IMMUNE FUNCTIONS DISRUPTING NORMAL DEVELOPMENT OF HORMONE-SENSITIVE ORGANS AND NEGATIVELY IMPACTING REPRODUCTIVE HEALTH. STUDIES INVESTIGATING MAMMARY GLAND DEVELOPMENT IN YOUNG ADULT MICE WILL HELP DEFINE HOW ADAPTATIONS TO SPACE TRAVEL CAN INFLUENCE THESE FUNDAMENTAL PROCESSES. THE DUCTAL NETWORK OF THE MAMMARY GLAND CONTAINS A NUMBER OF DIFFERENT CELL TYPES INCLUDING EPITHELIAL CELLS ADIPOCYTES IMMUNE CELLS VASCULAR ENDOTHELIAL CELLS AND FIBROBLASTS. SIGNALING BETWEEN THESE CELL TYPES IS HIGHLY SENSITIVE TO ENVIRONMENTAL PERTURBATIONS. IN ADDITION BOTH HORMONE AND IMMUNE RESPONSES HAVE BEEN SHOWN TO PLAY A CRITICAL ROLE IN DUCTAL NETWORK BRANCHING OF THE DEVELOPING MAMMARY GLAND. A COMBINATION OF NOVEL ASSAYS WILL BE USED TO UNDERSTAND HOW SPACE EXPOSURES IMPACT IMMUNE FUNCTION ADVERSELY AFFECTING MAMMARY GLAND DEVELOPMENT STEM CELL POPULATIONS AND THE REPRODUCTIVE ABILITY OF MICE. WE WILL TEST WHETHER SPACE ADAPTATION-INDUCED EPIGENETIC CHANGES IN THE OOCYTES OF MICE CORRELATE WITH REPRODUCTIVE ABILITY. WE HYPOTHESIZE THAT THE SPACE ENVIRONMENT WEAKENS THE IMMUNE SYSTEM AND ALTERS HORMONE BALANCE RESULTING IN ALTERATIONS IN NUMBER AND FUNCTION OF MAMMARY STEM CELLS AND DEVELOPMENT OF THE MAMMARY GLAND. ADDITIONALLY WE HYPOTHESIZE THAT EPIGENETIC CHANGES AS A RESULT OF SPACE EXPOSURE WILL AFFECT REPRODUCTIVE CAPABILITY AS COMPARED TO MICE ON EARTH. WE FURTHER PROPOSE THAT THE SENSITIVITY TO THESE EFFECTS IS DEPENDENT ON THE GENETIC BACKGROUND OF EXPOSED MICE. THESE STUDIES WILL AID IN DEFINING HOW ALTERATIONS IN IMMUNE FUNCTION FROM ADAPTATION TO SPACE TRAVEL AND SUBSEQUENT RE-ADAPTATION ON EARTH RESULTS IN DEFECTS IN ORGAN DEVELOPMENT REPRODUCTIVE ABILITY AND EPIGENETIC CHANGES AFFECTING THE FITNESS OF SUBSEQUENT GENERATIONS.