title: Overexpression of Bcl-W in the testis disrupts spermatogenesis: revelation of a role of BCL-W in male germ cell cycle control.
abstract: To explore physiological roles of BCL-W, a prosurvival member of the BCL-2 protein family, we generated transgenic (TG) mice overexpressing Bcl-w driven by a chicken beta-actin promoter. Male Bcl-w TG mice developed normally but were infertile. The adult TG testes displayed disrupted spermatogenesis with various severities ranging from thin seminiferous epithelium containing less germ cells to Sertoli cell-only appearance. No overpopulation of any type of germ cells was observed during testicular development. In contrast, the developing TG testes displayed decreased number of spermatogonia, degeneration, and detachment of spermatocytes and Sertoli cell vacuolization. The proliferative activity of germ cells was significantly reduced during testicular development and spermatogenesis, as determined by in vivo and in vitro 5'-bromo-2'deoxyuridine incorporation assays. Sertoli cells were structurally and functionally normal. The degenerating germ cells were TUNEL-negative and no typical apoptotic DNA ladder was detected. Our data suggest that regulated spatial and temporal expression of BCL-W is required for normal testicular development and spermatogenesis, and overexpression of BCL-W inhibits germ cell cycle entry and/or cell cycle progression leading to disrupted spermatogenesis.
authors.affiliation: Department of Physiology, University of Turku, Kiinamyllynkatu 10, FIN-20520, Turku, Finland. weiyan@bcm.tmc.edu.
authors.forename: Wei
authors.initials: W
authors.lastname: Yan
authors.forename: Jun-Xing
authors.initials: JX
authors.lastname: Huang
authors.forename: Anna-Stina
authors.initials: AS
authors.lastname: Lax
authors.forename: Lauri
authors.initials: L
authors.lastname: Pelliniemi
authors.forename: Eeva
authors.initials: E
authors.lastname: Salminen
authors.forename: Matti
authors.initials: M
authors.lastname: Poutanen
authors.forename: Jorma
authors.initials: J
authors.lastname: Toppari
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins; D053938:DNA Fragmentation; D020287:In Situ Nick-End Labeling; D007248:Infertility, Male / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008854:Microscopy, Electron; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D012670:Seminiferous Epithelium / Q000648:ultrastructure; D013091:Spermatogenesis / Q000502:physiology*; D013094:Spermatozoa / Q000378:metabolism*; D019089:Stem Cell Factor / Q000378:metabolism; D013737:Testis / Q000378:metabolism* / Q000473:pathology
chemical_list: D051017:Apoptosis Regulatory Proteins; C101155:Bcl2l2 protein, mouse; D011506:Proteins; D019089:Stem Cell Factor; D019009:Proto-Oncogene Proteins c-kit