Reverse transcriptase (RT) activity was recently detected in this laboratory in epididymal fluids from 4 mouse strains. Preliminary electronmicrographical studies revealed the presence of retrovirus-like particles in only two strains. This evidence indicates that (a) RT may be present in epididymal secretions independent of virus production and possibly associated with sperm, and (b) that infectious retroviruses may be more ubiquitous in apparently disease-free male mice than previously known. The research proposed will examine each of these hypotheses and provide the information neccessary to ultimately determine the physiologcal significance of RT in epididymal lumen. Experiments are designed to determine: (1) the identity of the putative viruses, (2) the distribution of virus in the reproductive tracts of males before and after castration and hormone replacement therapy, (3) if the viral infection is transferred to virus-free females at mating, (4) if RT is present in epididymal fluids in nonvirus producing strains, (5) if sperm from virus-free or virus-containing strains also contain RT activity, and (6) the nature of endogenous templates associated with the enzyme in the sperm and/or epididymal fluid. Enzymes will be purified and assayed by sensitive micro-procedures well established in this laboratory. Immunocytochemical studies at the light and electronmicroscope level will identify viral proteins and virus particles. The necessary histologic and immunocytochemical procedures are established and available. If the work confirms the presence of RT in epididymal fluids and/or sperm in the absence of virus, then the groundwork will be laid for future experiments to determine if reverse transcription plays a role in the male reproductive tract, in fertilization, and/or in early embryo development as proposed by Temin. Reverse transcription is now known to be a more common cell process than previously thought, but no information is available on RT activity in association with gametes. Alternatively, if RT is strictly associated with virus, the work will define the virus, the hormone influence on virus production, and the possible association of virus with fertilization and gestation. The presence of retrovirus in the male reproductive tract may relate to the suggestion of a normal biologic role for the virus in reproductive tracts of Swiss females. The work proposed is important to understanding if infectious virus and/or RT are transferred to females at mating and play a significant role in any aspect of the process of reproduction.
