The primary aim of this investigations to determine the biochemical conditions that are most likely to contribute to the emergence of malformed sperm during normal spermatogenesis in mice. To this date, nothing is known about the biochemical mechanisms responsible for their development either normally or following exposure to mutagenic, teratogenic and carcinogenic agents. It is known, however, that the fraction of abnormally-shaped sperm in an animal can be dramatically increased by exposing males to these deleterious agents. It seems warranted, therefore, that an investigation be initiated into the development of normal and abnormal sperm in an effort to reveal the biochemical component(s) most directly responsible for their deformation. Preliminary work in my laboratory indicates that post-testicular sperm maturation in Balb/C mice is radically different from that observed in SW mice. All the parameters thus far measured point to quantitative differences between Balb/C and Sw epididymal sperm. Since Balb/C mice contain an unusually high proportion of abnormally-shaped sperm *60%), it is our contention that the differences reflect partially assess this contention, we are presently involved in measuring individual epididymal sperm of both strains that we think is responsible for their morphological deformation. To date, we have identified clear differences in sulfhydryl and disulfide contents, in membrane protein contents and distribution, and in nuclear protein configuration. Based upon these preliminary data, we infer that the biochemical differences observed when comparing sperm from both strains have their origins in perturbations during spermatogenesis. Our specific aim, therefore, is to systematically compare spermatogenesis in both strains in terms of identifiable and measurable biochemical markers. These have been chosen because of their known involvement in the shaping of sperm cells. Students will be intimately involved in both phases of the project. The first phase will consist in determining the optimal conditions for isolating the various spermatogenic cell populations. This will specifically entail the testing of various methods for obtaining testicular cell suspensions (mechanical an/or enzymatic) and their separation through unit gravity sedimentation. The second phase will concentrate on staining with specific fluorochromes and measuring the stained cells. This last phase comprises the uses of an up-to-date implementation of computer-coupled image analysis. As usual, every effort will be made to assign each student a specific task within the total project. This not only encourages independence but also generates a needed sense of accomplishment. They will also be responsible for all aspects of the research including reading, writing, library research, and presentation locally and nationally.