title: Loss of protein phosphatase 1c{gamma} (PPP1CC) leads to impaired spermatogenesis associated with defects in chromatin condensation and acrosome development: an ultrastructural analysis.
abstract: Human male infertility affects approximately 5% of men, with one-third suffering from testicular failure, likely the result of an underlying genetic abnormality that disrupts spermatogenesis during development. Mouse models of male infertility such as the Ppp1cc knockout mouse display very similar phenotypes to humans with testicular failure. Male Ppp1cc mutant mice are sterile due to disruptions in spermatogenesis that begin during prepubertal testicular development, and continue into adulthood, often resulting in loss of germ cells to the point of Sertoli cell-only syndrome. The current study employs light and electron microscopy to identify new morphological abnormalities in Ppp1cc mutant seminiferous epithelium. This study reveals that germ cells become delayed in their development around stages VII and VIII of spermatogenesis. Loss of these cells likely results in the reduced numbers of elongating spermatids and spermatozoa previously observed in mutant animals. Interestingly, Ppp1cc mutants also display reduced numbers of spermatogonia compared with their wild-type counterparts. Using electron microscopy, we have shown that junction complexes in Ppp1cc mutants are ultrastructurally normal, and therefore do not contribute to the breakdown in tissue architecture seen in mutants. Electron microscopy revealed major acrosomal and chromatin condensation defects in Ppp1cc mutants. Our observations are discussed in the context of known molecular changes in Ppp1cc mutant testes.
authors.affiliation: Department of Cell and Systems Biology, University of Toronto, 25 Harbord Street, Toronto, Ontario, Canada M5S 3G5.
authors.forename: Nicole
authors.initials: N
authors.lastname: Forgione
authors.forename: A Wayne
authors.initials: AW
authors.lastname: Vogl
authors.forename: Susannah
authors.initials: S
authors.lastname: Varmuza
mesh_terms: D000177:Acrosome / Q000648:ultrastructure*; D000818:Animals; D002843:Chromatin / Q000648:ultrastructure*; D007248:Infertility, Male / Q000235:genetics / Q000473:pathology; D007365:Intercellular Junctions / Q000648:ultrastructure; D008297:Male; D051379:Mice; D008854:Microscopy, Electron; D009154:Mutation; D054645:Protein Phosphatase 1 / Q000235:genetics / Q000502:physiology*; D012670:Seminiferous Epithelium / Q000648:ultrastructure; D013076:Sperm Count; D013087:Spermatids / Q000648:ultrastructure; D013091:Spermatogenesis / Q000235:genetics / Q000502:physiology; D013093:Spermatogonia / Q000648:ultrastructure; D013094:Spermatozoa / Q000648:ultrastructure
chemical_list: D002843:Chromatin; C517103:Ppp1cc protein, mouse; D054645:Protein Phosphatase 1