The major function of sperm is the delivery of the paternal genome to the metaphase II oocyte, ensuring transmission of the genetic information to the next generation. For successful fertilization and healthy offspring, sperm
DNA must be protected from exogenous insults. This is achieved by packaging the sperm
DNA into a condensed
protamine-bound form, preceded by the precisely orchestrated removal of
histones and intermittent insertion and removal of transition
proteins. This remodeling process requires relaxation of
supercoiled DNA by transient formation of physiological strand breaks that spermatids, being haploid, cannot repair by homologous recombination. In somatic cells, the presence of
DNA strand breaks rapidly induces the formation of
poly(ADP-ribose) by nuclear
poly(ADP-ribose) polymerases, which in turn facilitates
DNA strand break signaling and assembly of DNA repair complexes. We reported earlier that chromatin remodeling steps during spermiogenesis trigger
poly(ADP-ribose) (PAR) formation. Here, we show that knockout mice deficient in PARP1, PARG (110-kDa isoform), or both display morphological and functional sperm abnormalities that are dependent on the individual genotypes, including residual
DNA strand breaks associated with varying degrees of
subfertility. The data presented highlight the importance of PAR metabolism, particularly PARG function, as a prerequisite of proper sperm
chromatin quality.