HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Rockett, J. C. Articles by Dix, D. J. Search for Related Content PubMed PubMed Citation Articles by Rockett, J. C. Articles by Dix, D. J. Agricola Articles by Rockett, J. C. Articles by Dix, D. J.

Effects of Hyperthermia on Spermatogenesis, Apoptosis, Gene Expression, and Fertility in Adult Male Mice¹

^a Reproductive Toxicology Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711 ^b Department of Anatomy, School of Medicine, Chiba University, Chiba 260-8670, Japan ^c Core Research for Evolutional Science and Technology CREST, Kawaguchi City, Saitama 332-0012, Japan

ABSTRACT

Testicular heat shock was used to characterize cellular and molecular mechanisms involved in male fertility. This model is relevant because heat shock proteins (HSPs) are required for spermatogenesis and also protect cells from environmental hazards such as heat, radiation, and chemicals. Cellular and molecular methods were used to characterize effects of testicular heat shock (43°C for 20 min) at different times posttreatment. Mating studies confirmed conclusions, based on histopathology, that spermatocytes are the most susceptible cell type. Apoptosis in spermatocytes was confirmed by TUNEL, and was temporally correlated with the expression of stress-inducible Hsp70-1 and Hsp70-3 proteins in spermatocytes. To further characterize gene expression networks associated with heat shock-induced effects, we used DNA microarrays to interrogate the expression of 2208 genes and thousands more expression sequence tags expressed in mouse testis. Of these genes, 27 were up-regulated and 151 were down-regulated after heat shock. Array data were concordant with the disruption of meiotic spermatogenesis, the heat-induced expression of HSPs, and an increase in apoptotic spermatocytes. Furthermore, array data indicated increased expression of four additional non-HSP stress response genes, and eight cell-adhesion, signaling, and signal-transduction genes. Decreased expression was recorded for 10 DNA repair and recombination genes; 9 protein synthesis, folding, and targeting genes; 9 cell cycle genes; 5 apoptosis genes; and 4 glutathione metabolism genes. Thus, the array data identify numerous candidate genes for further analysis in the heat-shocked testis model, and suggest multiple possible mechanisms for heat shock-induced infertility.

FOOTNOTES

First decision: 21 November 2000.

¹ The information in this document has been funded in part by the U.S. Environmental Protection Agency (EPA). It has been subjected to review by the National Health and Environmental Effects Research Laboratory and approved for publication. Approval does not signify that the contents reflect the views of EPA, nor does mention of trade names or commercial products constitute endorsement or recommendation for use. We thank Drs. James Allen and Jeffrey Welch (EPA) for scientific review of the manuscript prior to submission.

² Correspondence: David Dix, U.S. Environmental Protection Agency, Reproductive Toxicology Division (MD-72), Research Triangle Park, NC 27711. FAX: 919 541 4017; dix.david{at}epa.gov

This article has been cited by other articles:

				C. Paul, A. A Murray, N. Spears, and P. T K Saunders A single, mild, transient scrotal heat stress causes DNA damage, subfertility and impairs formation of blastocysts in mice Reproduction, July 1, 2008; 136(1): 73 - 84. [Abstract] [Full Text] [PDF]

				C. Paul, D. W. Melton, and P. T.K. Saunders Do heat stress and deficits in DNA repair pathways have a negative impact on male fertility? Mol. Hum. Reprod., January 1, 2008; 14(1): 1 - 8. [Abstract] [Full Text] [PDF]

				J. T. Selsby, S. Rother, S. Tsuda, O. Pracash, J. Quindry, and S. L. Dodd Intermittent hyperthermia enhances skeletal muscle regrowth and attenuates oxidative damage following reloading J Appl Physiol, April 1, 2007; 102(4): 1702 - 1707. [Abstract] [Full Text] [PDF]

				Y.-K. Kim, J. Suarez, Y. Hu, P. M. McDonough, C. Boer, D. J. Dix, and W. H. Dillmann Deletion of the Inducible 70-kDa Heat Shock Protein Genes in Mice Impairs Cardiac Contractile Function and Calcium Handling Associated With Hypertrophy Circulation, June 6, 2006; 113(22): 2589 - 2597. [Abstract] [Full Text] [PDF]

				J. Wistuba, C. M. Luetjens, R. Wesselmann, E. Nieschlag, M. Simoni, and S. Schlatt Meiosis in Autologous Ectopic Transplants of Immature Testicular Tissue Grafted to Callithrix jacchus Biol Reprod, April 1, 2006; 74(4): 706 - 713. [Abstract] [Full Text] [PDF]

				J. G. Farias, E. Bustos-Obregon, and J. G. Reyes Increase in Testicular Temperature and Vascularization Induced by Hypobaric Hypoxia in Rats J Androl, November 1, 2005; 26(6): 693 - 697. [Abstract] [Full Text] [PDF]

				A. Honaramooz, E. Behboodi, C. L. Hausler, S. Blash, S. Ayres, C. Azuma, Y. Echelard, and I. Dobrinski Depletion of Endogenous Germ Cells in Male Pigs and Goats in Preparation for Germ Cell Transplantation J Androl, November 1, 2005; 26(6): 698 - 705. [Abstract] [Full Text] [PDF]

				J. T. Selsby and S. L. Dodd Heat treatment reduces oxidative stress and protects muscle mass during immobilization Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2005; 289(1): R134 - R139. [Abstract] [Full Text] [PDF]

				S. Banks, S. A King, D S. Irvine, and P. T K Saunders Impact of a mild scrotal heat stress on DNA integrity in murine spermatozoa Reproduction, April 1, 2005; 129(4): 505 - 514. [Abstract] [Full Text] [PDF]

				N. Takano, H. Matusi, and T. Takahashi Granzyme N, a Novel Granzyme, Is Expressed in Spermatocytes and Spermatids of the Mouse Testis Biol Reprod, December 1, 2004; 71(6): 1785 - 1795. [Abstract] [Full Text] [PDF]

				C. Rohmer, J. R. David, B. Moreteau, and D. Joly Heat induced male sterility in Drosophila melanogaster: adaptive genetic variations among geographic populations and role of the Y chromosome J. Exp. Biol., July 15, 2004; 207(16): 2735 - 2743. [Abstract] [Full Text] [PDF]

				L. Somwaru, S. Li, L. Doglio, E. Goldberg, and B. R. Zirkin Heat-Induced Apoptosis of Mouse Meiotic Cells Is Suppressed by Ectopic Expression of Testis-Specific Calpastatin J Androl, July 1, 2004; 25(4): 506 - 513. [Abstract] [Full Text] [PDF]

				N. H. Ing, A. M. Laughlin, D. D. Varner, T. H. Welsh Jr., D. W. Forrest, T. L. Blanchard, and L. Johnson Gene Expression in the Spermatogenically Inactive "Dark" and Maturing "Light" Testicular Tissues of the Prepubertal Colt J Androl, July 1, 2004; 25(4): 535 - 544. [Abstract] [Full Text] [PDF]

				C. R. Hunt, D. J. Dix, G. G. Sharma, R. K. Pandita, A. Gupta, M. Funk, and T. K. Pandita Genomic Instability and Enhanced Radiosensitivity in Hsp70.1- and Hsp70.3-Deficient Mice Mol. Cell. Biol., January 15, 2004; 24(2): 899 - 911. [Abstract] [Full Text] [PDF]

				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]

				H. Izu, S. Inouye, M. Fujimoto, K. Shiraishi, K. Naito, and A. Nakai Heat Shock Transcription Factor 1 Is Involved in Quality-Control Mechanisms in Male Germ Cells Biol Reprod, January 1, 2004; 70(1): 18 - 24. [Abstract] [Full Text] [PDF]

				D. K. Tarka-Leeds, J. D. Suarez, N. L. Roberts, J. M. Rogers, M. P. Hardy, and G. R. Klinefelter Gestational Exposure to Ethane Dimethanesulfonate Permanently Alters Reproductive Competence in the CD-1 Mouse Biol Reprod, September 1, 2003; 69(3): 959 - 967. [Abstract] [Full Text] [PDF]

				Y. Lue, A. P. Sinha Hikim, C. Wang, A. Leung, and R. S. Swerdloff Functional Role of Inducible Nitric Oxide Synthase in the Induction of Male Germ Cell Apoptosis, Regulation of Sperm Number, and Determination of Testes Size: Evidence from Null Mutant Mice Endocrinology, July 1, 2003; 144(7): 3092 - 3100. [Abstract] [Full Text] [PDF]

				Z. Yu, R. Guo, Y. Ge, J. Ma, J. Guan, S. Li, X. Sun, S. Xue, and D. Han Gene Expression Profiles in Different Stages of Mouse Spermatogenic Cells During Spermatogenesis Biol Reprod, July 1, 2003; 69(1): 37 - 47. [Abstract] [Full Text] [PDF]

				D. J. McLean, P. J. Friel, D. Pouchnik, and M. D. Griswold Oligonucleotide Microarray Analysis of Gene Expression in Follicle-Stimulating Hormone-Treated Rat Sertoli Cells Mol. Endocrinol., December 1, 2002; 16(12): 2780 - 2792. [Abstract] [Full Text] [PDF]

				Y.-H. Lue, B. L. Lasley, L. S. Laughlin, R. S. Swerdloff, A. P. S. Hikim, A. Leung, J. W. Overstreet, and C. Wang Mild Testicular Hyperthermia Induces Profound Transitional Spermatogenic Suppression Through Increased Germ Cell Apoptosis in Adult Cynomolgus Monkeys (Macaca fascicularis)( J Androl, November 1, 2002; 23(6): 799 - 805. [Abstract] [Full Text] [PDF]

				L. A. Sonna, J. Fujita, S. L. Gaffin, and C. M. Lilly Molecular Biology of Thermoregulation: Invited Review: Effects of heat and cold stress on mammalian gene expression J Appl Physiol, April 1, 2002; 92(4): 1725 - 1742. [Abstract] [Full Text] [PDF]

				L. A. Sonna, S. L. Gaffin, R. E. Pratt, M. L. Cullivan, K. C. Angel, and C. M. Lilly Molecular Biology of Thermoregulation: Selected Contribution: Effect of acute heat shock on gene expression by human peripheral blood mononuclear cells J Appl Physiol, May 1, 2002; 92(5): 2208 - 2220. [Abstract] [Full Text] [PDF]