Chemically induced DNA damage and sperm and oocyte repair machinery: the story gets more interesting

Asian J Androl. 2015 May 19. doi: 10.4103/1008-682X.156118. Online ahead of print.


Assisted reproductive technologies have allowed us to bypass elusive questions of how spermatogenesis truly works so that end results, namely conception, can be achieved quickly and efficiently. Yet, reproductive biology, andrology, and molecular mutagenesis have not completely abandoned unanswered questions about how spermatogenesis unfolds, where things can go wrong in the process, and what are the impacts on the conceptus when sperm are somehow defective. Additional questions stem from the recognition that model systems are only approximations of how human reproduction actually happens in a world replete with extraneous exposures, from micronutrients to everyday chemicals. New evidence is adding to our understanding of how exceptionally stage-dependent spermatogenesis is, and how genotoxic exposures at exact stages differentially affect sperm cells. Recently reported new mouse model evidence demonstrates that postfertilization, oocytes misrepair sperm DNA defects that allow chromosomal structural aberrations to persist in the conceptus. These findings give new perspectives on both intrinsic actions of DNA repair checkpoints and on critical windows of sperm vulnerability to mutagenicity and toxicity.