title: Disruption of poly(ADP-ribose) homeostasis affects spermiogenesis and sperm chromatin integrity in mice.
abstract: 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.
authors.affiliation: Department of Animal Biology and Mari Lowe Center for Comparative Oncology, University of Pennsylvania School of Veterinary Medicine, Kennett Square, Pennsylvania 19348, USA. meyerg@vet.upenn.edu
authors.forename: Mirella L
authors.initials: ML
authors.lastname: Meyer-Ficca
authors.forename: Julia
authors.initials: J
authors.lastname: Lonchar
authors.forename: Christine
authors.initials: C
authors.lastname: Credidio
authors.forename: Motomasa
authors.initials: M
authors.lastname: Ihara
authors.forename: Yun
authors.initials: Y
authors.lastname: Li
authors.forename: Zhao-Qi
authors.initials: ZQ
authors.lastname: Wang
authors.forename: Ralph G
authors.initials: RG
authors.lastname: Meyer
mesh_terms: D000818:Animals; D002843:Chromatin / Q000235:genetics / Q000378:metabolism*; D053960:DNA Breaks; D042822:Genomic Instability / Q000235:genetics*; D006706:Homeostasis / Q000235:genetics*; D007248:Infertility, Male / Q000235:genetics; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D011064:Poly Adenosine Diphosphate Ribose / Q000378:metabolism*; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics* / Q000378:metabolism; D013081:Sperm Motility / Q000235:genetics / Q000502:physiology; D013091:Spermatogenesis / Q000235:genetics*; D013094:Spermatozoa / Q000378:metabolism
chemical_list: D002843:Chromatin; D007527:Isoenzymes; D011064:Poly Adenosine Diphosphate Ribose; D011065:Poly(ADP-ribose) Polymerases