| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Regular Article |
a Department of Physiology, Southern Illinois University School of Medicine, Carbondale, Illinois 62901-6512
b Department of Biochemistry and Cellular and Molecular Biology, University of Tennessee, Knoxville, Tennessee 37996
c Center for Molecular Medicine, Emory University School of Medicine, Atlanta, Georgia 30322
d Graduate Program in Biochemistry, Cell and Developmental Biology, Emory University, Atlanta, Georgia 30322
ABSTRACT
Bclw is a death-protecting member of the Bcl2 family of apoptosis-regulating proteins. Mice that are mutant for Bclw display progressive and nearly complete testicular degeneration. We performed a morphometric evaluation of testicular histopathology in Bclw-deficient male mice between 9 days postnatal (p9) through 1 yr of age. Germ cell loss began by p22, with only few germ cells remaining beyond 7 mo of age. A complete block to elongated spermatid development at step 13 occurred during the first wave of spermatogenesis, whereas other types of germ cells were lost sporadically. Depletion of Sertoli cells commenced between p20 and p23 and continued until 1 yr of age, when few, if any, Sertoli cells remained. Mitochondria appeared to be swollen and the cytoplasm dense by electron microscopy, but degenerating Bclw-deficient Sertoli cells failed to display classical features of apoptosis, such as chromatin condensation and nuclear fragmentation. Macrophages entered seminiferous tubules and formed foreign-body giant cells that engulfed and phagocytosed the degenerated Sertoli cells. Leydig cell hyperplasia was evident between 3 and 5 mo of age. However, beginning at 7 mo of age, Leydig cells underwent apoptosis, with dead cells being phagocytosed by macrophages. The aforementioned cell losses culminated in a testis-containing vasculature, intertubular phagocytic cells, and peritubular cell "ghosts." An RNA in situ hybridization study indicates that Bclw is expressed in Sertoli cells in the adult mouse testis. Consequently, the diploid germ cell death may be an indirect effect of defective Sertoli cell function. Western analysis was used to confirm that Bclw is not expressed in spermatids; thus, loss of this cell type most likely results from defective Sertoli cell function. Because Bclw does not appear to be expressed in Leydig cells, loss of Leydig cells in Bclw-deficient mice may result from depletion of Sertoli cells. Bclw-deficient mice serve as a unique model to study homeostasis of cell populations in the testis.
First decision: 17 October 2000.
1 Supported by grants from the NIH (HD36437 to G.R.M. and HD35494 to L.D.R.). Part of this work was performed in the laboratory of M.A. Handel with support from HD31376.
2 Correspondence: Lonnie D. Russell, Dept. of Physiology, Southern Illinois University, Life Sci II, Room 174, Lincoln Drive, Carbondale, IL 62901-6501. FAX: 618 453 1517; lrussell{at}siumed.edu Grant R. MacGregor, Center for Molecular Medicine, Emory University School of Medicine, 1462 Clifton Rd. NE, 403-E, Atlanta, GA 30322. FAX: 404 727 8367; gmacgre{at}emory.edu
3 Current address: Dept. of Anatomy and Cell Biology, Marshall University, Huntington, WV 25704.
This article has been cited by other articles:
|
|
 |
|
  P J O'Shaughnessy, L Hu, and P J Baker Effect of germ cell depletion on levels of specific mRNA transcripts in mouse Sertoli cells and Leydig cells Reproduction, June 1, 2008; 135(6): 839 - 850. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. J. O'SHAUGHNESSY, P. J. BAKER, and H. JOHNSTON Neuroendocrine Regulation of Leydig Cell Development Ann. N.Y. Acad. Sci., December 1, 2005; 1061(1): 109 - 119. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. M. Segatelli, L. R. Franca, P. F. F. Pinheiro, C. C. D. Alemida, M. Martinez, and F. E. Martinez Spermatogenic Cycle Length and Spermatogenic Efficiency in the Gerbil (Meriones unguiculatus) J Androl, November 1, 2004; 25(6): 872 - 880. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Berthet, A.-M. Morera, M.-J. Asensio, M.-A. Chauvin, A.-P. Morel, F. Dijoud, J.-P. Magaud, P. Durand, and J.-P. Rouault CCR4-Associated Factor CAF1 Is an Essential Factor for Spermatogenesis Mol. Cell. Biol., July 1, 2004; 24(13): 5808 - 5820. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. D. Show, J. S. Folmer, M. D. Anway, and B. R. Zirkin Testicular Expression and Distribution of the Rat Bcl2 Modifying Factor in Response to Reduced Intratesticular Testosterone Biol Reprod, April 1, 2004; 70(4): 1153 - 1161. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Johnston, P. J. Baker, M. Abel, H. M. Charlton, G. Jackson, L. Fleming, T. R. Kumar, and P. J. O'Shaughnessy Regulation of Sertoli Cell Number and Activity by Follicle-Stimulating Hormone and Androgen during Postnatal Development in the Mouse Endocrinology, January 1, 2004; 145(1): 318 - 329. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Yan, J.-X. Huang, A.-S. Lax, L. Pelliniemi, E. Salminen, M. Poutanen, and J. Toppari Overexpression of Bcl-w in the Testis Disrupts Spermatogenesis: Revelation of a Role of BCL-W in Male Germ Cell Cycle Control Mol. Endocrinol., September 1, 2003; 17(9): 1868 - 1879. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P.J. O'Shaughnessy, L. Fleming, P.J. Baker, G. Jackson, and H. Johnston Identification of Developmentally Regulated Genes in the Somatic Cells of the Mouse Testis Using Serial Analysis of Gene Expression Biol Reprod, September 1, 2003; 69(3): 797 - 808. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Wise, D. D. Lunstra, G. A. Rohrer, and J. J. Ford Relationships of testicular iron and ferritin concentrations with testicular weight and sperm production in boars J Anim Sci, February 1, 2003; 81(2): 503 - 511. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. J. Baker, P. Pakarinen, I. T. Huhtaniemi, M. H. Abel, H. M. Charlton, T. R. Kumar, and P. J. O'Shaughnessy Failure of Normal Leydig Cell Development in Follicle-Stimulating Hormone (FSH) Receptor-Deficient Mice, But Not FSH{beta}-Deficient Mice: Role for Constitutive FSH Receptor Activity Endocrinology, January 1, 2003; 144(1): 138 - 145. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. G. Parreira, R. C.N. Melo, and L. D. Russell Relationship of Sertoli-Sertoli Tight Junctions to Ectoplasmic Specialization in Conventional and En Face Views Biol Reprod, October 1, 2002; 67(4): 1232 - 1241. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. S. Neves, H. Chiarini-Garcia, and L. R. Franca Comparative Testis Morphometry and Seminiferous Epithelium Cycle Length in Donkeys and Mules Biol Reprod, July 1, 2002; 67(1): 247 - 255. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
