Presenter(s): Fountane Chan
Faculty Mentor(s): Diana Libuda & Nicole Kurhanewicz
Oral Session 3 M
Poster 47
Session: Sciences
Half of infertility cases worldwide involve male-factor subfertility. As awareness and frequency of male infertility has grown, it is increasingly important to understand the underlying mechanisms of these major human health concerns. Developing sperm are particularly sensitive to fluctuations in temperature, requiring a narrow isotherm of 2-7°C below core body temperature. Although both oocytes and spermatocytes undergo meiosis, the specialized form of cell division that produces haploid sex cells, elevated gonadal temperatures have been shown both to impair only male fertility and produce excess DNA damage specifically in spermatocytes. Preliminary work using the powerful roundworm model Caenorhabditis elegans suggests the Piwi-piRNA pathway, a highly conserved genome maintenance pathway, is involved in temperature-induced DNA damage. Absence of worm-specific Argonaute proteins (WAGO), primary effector proteins of the Piwi pathway, results in considerably elevated DNA damage upon heat-shock. Interestingly, a panel of mutants deficient in the C. elegans Piwi protein, PRG-1, which functions upstream of WAGOs, demonstrate highly variable degrees of heat-induced DNA damage. This variability is likely due to acquired mutations stemming from inadequate germline surveillance over multiple generations. To circumvent this issue by controlling the number of generations a strain is without PRG-1, we generated a conditional knockdown mutant of PRG-1. Utilizing this mutant, we found that in the absence of PRG-1 after one generation, spermatocytes demonstrate exacerbated levels of heat-induced DNA damage, similar to WAGO null mutants. Taken together, my data suggest a key role for PRG-1 and male-specific components of the Piwi pathway in heat-induced DNA damage in spermatocytes.