help button home button Endocrine Society Endocrinology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Lee, J.
Right arrow Articles by Boekelheide, K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lee, J.
Right arrow Articles by Boekelheide, K.
Endocrinology Vol. 140, No. 2 852-858
Copyright © 1999 by The Endocrine Society

ARTICLES

The Fas System, a Regulator of Testicular Germ Cell Apoptosis, Is Differentially Up-Regulated in Sertoli Cell Versus Germ Cell Injury of the Testis1

Jeongwu Lee, John H. Richburg2, Elizabeth B. Shipp, Marvin L. Meistrich and Kim Boekelheide3

Department of Pathology and Laboratory Medicine, Brown University (J.L., E.B.S., K.B.), Providence, Rhode Island 02912; and the Department of Experimental Radiation Oncology, M. D. Anderson Cancer Center (M.L.M.), Houston, Texas 77030

Address all correspondence and requests for reprints to: Kim Boekelheide, M.D., Ph.D., Department of Pathology and Laboratory Medicine, Brown University, Box G-B518, Providence, Rhode Island 02912. E-mail: kim_boekelheide{at}brown.edu

Sertoli cells, the supportive cells in the seminiferous epithelium, orchestrate spermatogenesis by providing structural and nutritional support to germ cells. In the rat, physiological apoptosis occurs continuously to limit the size of the germ cell population to numbers that can be adequately supported. This form of germ cell death is exaggerated after testicular insults such as toxicant treatment, radiation, and heat exposure. The Fas system has been proposed as a key regulator of the activation of germ cell apoptosis. According to this model, Fas ligand (FasL) and Fas, expressed by Sertoli cells and germ cells, respectively, respond to environmental conditions and initiate germ cell death. To assess the role of the Fas system in various testicular injury models, a semiquantitative RT-PCR technique was used to evaluate the expression kinetics of both FasL and Fas after induction of massive germ cell death. Radiation exposure, which targets actively dividing germ cells, produced an up-regulation of Fas gene expression, but not FasL gene expression. However, administration of mono-(2-ethylhexyl)phthalate and 2,5-hexanedione, two widely studied Sertoli cell toxicants, resulted in up-regulated expression of both FasL and Fas. These data support the following hypotheses: 1) up-regulation of Fas is a common and critical step for initiating germ cell death in vivo; and 2) if Sertoli cells are injured, Sertoli cells up-regulate FasL to eliminate Fas-positive germ cells, which cannot be supported adequately.




This article has been cited by other articles:


Home page
 EndocrinologyHome page
G. Shetty, S. H. Shao, and C. C. Y. Weng
p53-Dependent Apoptosis in the Inhibition of Spermatogonial Differentiation in Juvenile Spermatogonial Depletion (Utp14bjsd) Mice
Endocrinology, June 1, 2008; 149(6): 2773 - 2781.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
K. M. Naugler, K. A. Baer, and M. J. Ropeleski
Interleukin-11 antagonizes Fas ligand-mediated apoptosis in IEC-18 intestinal epithelial crypt cells: role of MEK and Akt-dependent signaling
Am J Physiol Gastrointest Liver Physiol, March 1, 2008; 294(3): G728 - G737.
[Abstract] [Full Text] [PDF]

Home page
 Mol Hum ReprodHome page
S. Marchiani, L. Tamburrino, A. Maoggi, G.B. Vannelli, G. Forti, E. Baldi, and M. Muratori
Characterization of M540 bodies in human semen: evidence that they are apoptotic bodies
Mol. Hum. Reprod., September 1, 2007; 13(9): 621 - 631.
[Abstract] [Full Text] [PDF]

Home page
 ReproductionHome page
S C Mizrak, F Renault-Mihara, M Parraga, J Bogerd, H J G van de Kant, P P Lopez-Casas, M Paz, J del Mazo, and D G de Rooij
Phosphoprotein enriched in astrocytes-15 is expressed in mouse testis and protects spermatocytes from apoptosis
Reproduction, April 1, 2007; 133(4): 743 - 751.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
P.-L. Yao, Y.-C. Lin, P. Sawhney, and J. H. Richburg
Transcriptional Regulation of FasL Expression and Participation of sTNF-{alpha} in Response to Sertoli Cell Injury
J. Biol. Chem., February 23, 2007; 282(8): 5420 - 5431.
[Abstract] [Full Text] [PDF]

Home page
 J AndrolHome page
E. Morales, C. Ferrer, A. Zuasti, J. C. Garcia-Borron, M. Canteras, and L. M. Pastor
Apoptosis and Molecular Pathways in the Seminiferous Epithelium of Aged and Photoinhibited Syrian Hamsters (Mesocricetus auratus)
J Androl, January 1, 2007; 28(1): 123 - 135.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
T. Rasoulpour, K. DiPalma, B. Kolvek, and M. Hixon
Akt1 Suppresses Radiation-Induced Germ Cell Apoptosis in Vivo
Endocrinology, September 1, 2006; 147(9): 4213 - 4221.
[Abstract] [Full Text] [PDF]

Home page
 Biol. Reprod.Home page
Y. Chandrasekaran, C. M. Mckee, Y. Ye, and J. H. Richburg
Influence of TRP53 Status on FAS Membrane Localization, CFLAR (c-FLIP) Ubiquitinylation, and Sensitivity of GC-2spd (ts) Cells to Undergo FAS-Mediated Apoptosis
Biol Reprod, March 1, 2006; 74(3): 560 - 568.
[Abstract] [Full Text] [PDF]

Home page
 J Natl Cancer Inst MonogrHome page
K. Boekelheide
Mechanisms of Toxic Damage to Spermatogenesis
J Natl Cancer Inst Monographs, March 1, 2005; 2005(34): 6 - 8.
[Abstract] [Full Text] [PDF]

Home page
 Biol. Reprod.Home page
R. J. Rasoulpour and K. Boekelheide
NF-{kappa}B Is Activated in the Rat Testis Following Exposure to Mono-(2-Ethylhexyl) Phthalate
Biol Reprod, February 1, 2005; 72(2): 479 - 486.
[Abstract] [Full Text] [PDF]

Home page
 Biol. Reprod.Home page
Y. Chandrasekaran and J. H. Richburg
The p53 Protein Influences the Sensitivity of Testicular Germ Cells to Mono-(2-Ethylhexyl) Phthalate-Induced Apoptosis by Increasing the Membrane Levels of Fas and DR5 and Decreasing the Intracellular Amount of c-FLIP
Biol Reprod, January 1, 2005; 72(1): 206 - 213.
[Abstract] [Full Text] [PDF]

Home page
 J AndrolHome page
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]

Home page
 Mol Hum ReprodHome page
R. Grataroli, D. Vindrieux, J. Selva, C. Felsenheld, A. Ruffion, M. Decaussin, and M. Benahmed
Characterization of tumour necrosis factor-{alpha}-related apoptosis-inducing ligand and its receptors in the adult human testis
Mol. Hum. Reprod., February 1, 2004; 10(2): 123 - 128.
[Abstract] [Full Text] [PDF]

Home page
 Hum Reprod UpdateHome page
T. M. Said, U. Paasch, H.-J. Glander, and A. Agarwal
Role of caspases in male infertility
Hum. Reprod. Update, January 1, 2004; 10(1): 39 - 51.
[Abstract] [Full Text] [PDF]

Home page
 J AndrolHome page
Z. Zhang, R.V. Short, T. Meehan, D.M. de Kretser, M.B. Renfree, and K.L. Loveland
Functional Analysis of the Cooled Rat Testis
J Androl, January 1, 2004; 25(1): 57 - 68.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol SciHome page
M. L. Meistrich, G. Wilson, K. L. Porter, I. Huhtaniemi, G. Shetty, and G. A. Shuttlesworth
Restoration of Spermatogenesis in Dibromochloropropane (DBCP)-Treated Rats by Hormone Suppression
Toxicol. Sci., December 1, 2003; 76(2): 418 - 426.
[Abstract] [Full Text] [PDF]

Home page
 Biol. Reprod.Home page
H. Li and K. H. Kim
Effects of Mono-(2-Ethylhexyl) Phthalate on Fetal and Neonatal Rat Testis Organ Cultures
Biol Reprod, December 1, 2003; 69(6): 1964 - 1972.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
A. P. S. Hikim, Y. Lue, C. M. Yamamoto, Y. Vera, S. Rodriguez, P. H. Yen, K. Soeng, C. Wang, and R. S. Swerdloff
Key Apoptotic Pathways for Heat-Induced Programmed Germ Cell Death in the Testis
Endocrinology, July 1, 2003; 144(7): 3167 - 3175.
[Abstract] [Full Text] [PDF]

Home page
 J AndrolHome page
M. L. Meistrich and G. Shetty
Inhibition of Spermatogonial Differentiation by Testosterone
J Androl, March 1, 2003; 24(2): 135 - 148.
[Full Text] [PDF]

Home page
 Mol. Biol. CellHome page
L. M. Budde, C. Wu, C. Tilman, I. Douglas, and S. Ghosh
Regulation of Ikappa Bbeta Expression in Testis
Mol. Biol. Cell, December 1, 2002; 13(12): 4179 - 4194.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
S. Narisawa, N. B. Hecht, E. Goldberg, K. M. Boatright, J. C. Reed, and J. L. Millan
Testis-Specific Cytochrome c-Null Mice Produce Functional Sperm but Undergo Early Testicular Atrophy
Mol. Cell. Biol., August 1, 2002; 22(15): 5554 - 5562.
[Abstract] [Full Text] [PDF]

Home page
 Hum ReprodHome page
J. Tesarik, F. Martinez, L. Rienzi, M. Iacobelli, F. Ubaldi, C. Mendoza, and E. Greco
In-vitro effects of FSH and testosterone withdrawal on caspase activation and DNA fragmentation in different cell types of human seminiferous epithelium
Hum. Reprod., July 1, 2002; 17(7): 1811 - 1819.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol PatholHome page
L. L. Lanning, D. M. Creasy, R. E. Chapin, P. C. Mann, N. J. Barlow, K. S. Regan, and D. G. Goodman
Recommended Approaches for the Evaluation of Testicular and Epididymal Toxicity
Toxicol Pathol, June 1, 2002; 30(4): 507 - 520.
[PDF]

Home page
 Biol. Reprod.Home page
R. Grataroli, D. Vindrieux, A. Gougeon, and M. Benahmed
Expression of Tumor Necrosis Factor-{alpha}-Related Apoptosis-Inducing Ligand and Its Receptors in Rat Testis During Development
Biol Reprod, June 1, 2002; 66(6): 1707 - 1715.
[Abstract] [Full Text] [PDF]

Home page
 Biol. Reprod.Home page
M. Embree-Ku, D. Venturini, and K. Boekelheide
Fas Is Involved in the p53-Dependent Apoptotic Response to Ionizing Radiation in Mouse Testis
Biol Reprod, May 1, 2002; 66(5): 1456 - 1461.
[Abstract] [Full Text]

Home page
 Mol Hum ReprodHome page
S. Francavilla, P. D'Abrizio, G. Cordeschi, F. Pelliccione, S. Necozione, S. Ulisse, G. Properzi, and F. Francavilla
Fas expression correlates with human germ cell degeneration in meiotic and post-meiotic arrest of spermatogenesis
Mol. Hum. Reprod., March 1, 2002; 8(3): 213 - 220.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
V. Pentikainen, L. Suomalainen, K. Erkkila, E. Martelin, M. Parvinen, M. O. Pentikainen, and L. Dunkel
Nuclear Factor-{kappa}B Activation in Human Testicular Apoptosis
Am. J. Pathol., January 1, 2002; 160(1): 205 - 218.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
Y. Morishima, Y. Gotoh, J. Zieg, T. Barrett, H. Takano, R. Flavell, R. J. Davis, Y. Shirasaki, and M. E. Greenberg
{beta}-Amyloid Induces Neuronal Apoptosis Via a Mechanism that Involves the c-Jun N-Terminal Kinase Pathway and the Induction of Fas Ligand
J. Neurosci., October 1, 2001; 21(19): 7551 - 7560.
[Abstract] [Full Text] [PDF]

Home page
 J. Leukoc. Biol.Home page
B. L. Jaber, M. C Perianayagam, V. S Balakrishnan, A. J King, and B. J. G. Pereira
Mechanisms of neutrophil apoptosis in uremia and relevance of the Fas (APO-1, CD95)/Fas ligand system
J. Leukoc. Biol., June 1, 2001; 69(6): 1006 - 1012.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
M. J. Scobey, S. Bertera, J. P. Somers, S. C. Watkins, A. J. Zeleznik, and W. H. Walker
Delivery of a Cyclic Adenosine 3',5'-Monophosphate Response Element-Binding Protein (CREB) Mutant to Seminiferous Tubules Results in Impaired Spermatogenesis
Endocrinology, February 1, 2001; 142(2): 948 - 954.
[Abstract] [Full Text] [PDF]

Home page
 Biol. Reprod.Home page
K. A. Young, G. F. Ball, and R. J. Nelson
Photoperiod-Induced Testicular Apoptosis in European Starlings (Sturnus vulgaris)
Biol Reprod, February 1, 2001; 64(2): 706 - 713.
[Abstract] [Full Text]

Home page
 Toxicol PatholHome page
D. M. Creasy
Pathogenesis of Male Reproductive Toxicity
Toxicol Pathol, January 1, 2001; 29(1): 64 - 76.
[Abstract] [PDF]

Home page
 Exp. Biol. Med.Home page
K. Boekelheide, S. L. Fleming, K. J. Johnson, S. R. Patel, and H. A. Schoenfeld
Role of Sertoli Cells in Injury-Associated Testicular Germ Cell Apoptosis
Experimental Biology and Medicine, November 1, 2000; 225(2): 105 - 115.
[Abstract] [Full Text]

Home page
 Hum ReprodHome page
H. Yazawa, I. Sasagawa, and T. Nakada
Apoptosis of testicular germ cells induced by exogenous glucocorticoid in rats
Hum. Reprod., September 1, 2000; 15(9): 1917 - 1920.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
S. Francavilla, P. D’Abrizio, N. Rucci, G. Silvano, G. Properzi, E. Straface, G. Cordeschi, S. Necozione, L. Gnessi, M. Arizzi, et al.
Fas and Fas Ligand Expression in Fetal and Adult Human Testis with Normal or Deranged Spermatogenesis
J. Clin. Endocrinol. Metab., August 1, 2000; 85(8): 2692 - 2700.
[Abstract] [Full Text]

Home page
 EndocrinologyHome page
Y. Lue, A. P. Sinha Hikim, C. Wang, M. Im, A. Leung, and R. S. Swerdloff
Testicular Heat Exposure Enhances the Suppression of Spermatogenesis by Testosterone in Rats: The "Two-Hit" Approach to Male Contraceptive Development
Endocrinology, April 1, 2000; 141(4): 1414 - 1424.
[Abstract] [Full Text] [PDF]

Home page
 Hum ReprodHome page
L. Gandini, F. Lombardo, D. Paoli, L. Caponecchia, G. Familiari, C. Verlengia, F. Dondero, and A. Lenzi
Study of apoptotic DNA fragmentation in human spermatozoa
Hum. Reprod., April 1, 2000; 15(4): 830 - 839.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
J. H. Richburg, A. Nanez, L. R. Williams, M. E. Embree, and K. Boekelheide
Sensitivity of Testicular Germ Cells to Toxicant-Induced Apoptosis in gld Mice That Express a Nonfunctional Form of Fas Ligand
Endocrinology, February 1, 2000; 141(2): 787 - 793.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals
Copyright © 1999 by The Endocrine Society