title: Spermatid head elongation with normal nuclear shaping requires ADP-ribosyltransferase PARP11 (ARTD11) in mice.
abstract: Sperm are highly differentiated cells characterized by their species-specific nuclear shapes and extremely condensed chromatin. Abnormal head shapes represent a form of teratozoospermia that can impair fertilization capacity. This study shows that poly(ADP-ribose) polymerase-11 (ARTD11/PARP11), a member of the ADP-ribosyltransferase (ARTD) family, is expressed preferentially in spermatids undergoing nuclear condensation and differentiation. Deletion of the Parp11 gene results in teratozoospermia and male infertility in mice due to the formation of abnormally shaped fertilization-incompetent sperm, despite normal testis weights and sperm counts. At the subcellular level, PARP11-deficient elongating spermatids reveal structural defects in the nuclear envelope and chromatin detachment associated with abnormal nuclear shaping, suggesting functional relevance of PARP11 for nuclear envelope stability and nuclear reorganization during spermiogenesis. In vitro, PARP11 exhibits mono(ADP-ribosyl)ation activity with the ability to ADP-ribosylate itself. In transfected somatic cells, PARP11 colocalizes with nuclear pore components, such as NUP153. Amino acids Y77, Q86, and R95 in the N-terminal WWE domain, as well as presence of the catalytic domain, are essential for colocalization of PARP11 with the nuclear envelope, but catalytic activity of the protein is not required for colocalization with NUP153. This study demonstrates that PARP11 is a novel enzyme important for proper sperm head shaping and identifies it as a potential factor involved in idiopathic mammalian teratozoospermia.
authors: Department of Animal Dairy and Veterinary Sciences, College of Agriculture and Applied Sciences, Utah Agricultural Experimental Station, Utah State University, Logan, Utah Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania mirella.meyer@usu.edu.
authors: Mirella L
authors: ML
authors: Meyer-Ficca
authors: Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors: Motomasa
authors: M
authors: Ihara
authors: Department of Animal Dairy and Veterinary Sciences, College of Agriculture and Applied Sciences, Utah Agricultural Experimental Station, Utah State University, Logan, Utah Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors: Jessica J
authors: JJ
authors: Bader
authors: Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors: N Adrian
authors: NA
authors: Leu
authors: Molecular Toxicology Group, Department of Biology, University of Konstanz, Konstanz, Germany.
authors: Sascha
authors: S
authors: Beneke
authors: Department of Animal Dairy and Veterinary Sciences, College of Agriculture and Applied Sciences, Utah Agricultural Experimental Station, Utah State University, Logan, Utah Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors: Ralph G
authors: RG
authors: Meyer
mesh_terms: D000818:Animals; D002467:Cell Nucleus / Q000473:pathology / Q000502:physiology; D053144:Cell Nucleus Shape / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D007248:Infertility, Male / Q000235:genetics / Q000503:physiopathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009685:Nuclear Envelope / Q000502:physiology; D010641:Phenotype; D011065:Poly(ADP-ribose) Polymerases / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D013075:Sperm Capacitation / Q000235:genetics / Q000502:physiology; D013077:Sperm Head / Q000473:pathology / Q000502:physiology*; D013087:Spermatids / Q000166:cytology / Q000502:physiology*; D013091:Spermatogenesis / Q000235:genetics / Q000502:physiology*
chemical_list: D011065:Poly(ADP-ribose) Polymerases; C000605039:poly(ADP-ribose) polymerase-11, mouse
keywords: ADP-ribose; ARTD11; MAR; PAR; PARG; PARP; PARP11; WWE domain; acrosome; condensation; gametogenesis; infertility; male infertility; mono(ADP-ribosyl)ation; mouse; nuclear envelope; poly(ADP-ribosyl)ation; sperm; sperm differentiation; spermatid; spermatogenesis; spermiogenesis; teratozoospermia; testis; transgenic/knockout model