title: CHD5 is required for spermiogenesis and chromatin condensation.
abstract: Haploid spermatids undergo extensive cellular, molecular and morphological changes to form spermatozoa during spermiogenesis. Abnormalities in these steps can lead to serious male fertility problems, from oligospermia to complete azoospermia. CHD5 is a chromatin-remodeling nuclear protein expressed almost exclusively in the brain and testis. Male Chd5 knockout (KO) mice have deregulated spermatogenesis, characterized by immature sloughing of spermatids, spermiation failure, disorganization of the spermatogenic cycle and abnormal head morphology in elongating spermatids. This results in the inappropriate placement and juxtaposition of germ cell types within the epithelium. Sperm that did enter the epididymis displayed irregular shaped sperm heads, and retained cytoplasmic components. These sperm also stained positively for acidic aniline, indicating improper removal of histones and lack of proper chromatin condensation. Electron microscopy showed that spermatids in the seminiferous tubules of Chd5 KO mice have extensive nuclear deformation, with irregular shaped heads of elongated spermatids, and lack the progression of chromatin condensation in an anterior-to-posterior direction. However, the mRNA expression levels of other important genes controlling spermatogenesis were not affected. Chd5 KO mice also showed decreased H4 hyperacetylation beginning at stage IX, step 9, which is vital for the histone-transition protein replacement in spermiogenesis. Our data indicate that CHD5 is required for normal spermiogenesis, especially for spermatid chromatin condensation.
authors.affiliation: Division of Oncology, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, United States.
authors.forename: Tiangang
authors.initials: T
authors.lastname: Zhuang
authors.affiliation: Department of Comparative Biosciences, College of Veterinary Medicine, University of Illinois at Urbana-Champaign, Urbana, IL 61802, United States.
authors.forename: Rex A
authors.initials: RA
authors.lastname: Hess
authors.affiliation: Division of Oncology, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, United States.
authors.forename: Venkatadri
authors.initials: V
authors.lastname: Kolla
authors.affiliation: Division of Oncology, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, United States.
authors.forename: Mayumi
authors.initials: M
authors.lastname: Higashi
authors.affiliation: Penn Gene Targeting Service, University of Pennsylvania, Philadelphia, PA 19104, United States.
authors.forename: Tobias D
authors.initials: TD
authors.lastname: Raabe
authors.affiliation: Division of Oncology, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, United States; The Department of Pediatrics, Perelman School of Medicine, Philadelphia, PA 19104, United States. Electronic address: Brodeur@email.chop.edu.
authors.forename: Garrett M
authors.initials: GM
authors.lastname: Brodeur
mesh_terms: D000818:Animals; D002843:Chromatin / Q000235:genetics / Q000648:ultrastructure*; D004265:DNA Helicases / Q000235:genetics*; D006657:Histones / Q000235:genetics / Q000378:metabolism; D007248:Infertility, Male / Q000235:genetics*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008854:Microscopy, Electron; D013087:Spermatids / Q000648:ultrastructure; D013091:Spermatogenesis / Q000235:genetics*; D013094:Spermatozoa / Q000378:metabolism / Q000648:ultrastructure; D013737:Testis / Q000254:growth & development / Q000378:metabolism / Q000648:ultrastructure
chemical_list: D002843:Chromatin; D006657:Histones; D004265:DNA Helicases; C583981:Chd5 protein, mouse
keywords: CHD5; Chromatin condensation; Histone modification; Infertility; Spermatogenesis; Spermiogenesis