This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services 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 Fenic, I. Articles by Steger, K. Search for Related Content PubMed PubMed Citation Articles by Fenic, I. Articles by Steger, K.

In Vivo Effects of Histone-Deacetylase Inhibitor Trichostatin-A on Murine Spermatogenesis

KLAUS FAILING

KLAUS STEGER

From the ^* Institute of Veterinary Anatomy, Histology and Embryology, and Institute of Veterinary Physiology, Department of Biomathematics, and Department of Urology and Pediatric Urology, University of Giessen, Germany.

Correspondence to: PD Dr Klaus Steger, Klinich für Urologie und Kinderurologie, Rudolf-Buchheim, Straße 7, 35385 Giessen, Germany (e-mail: Klaus.Steger{at}chiru-med.uni-giessen.de).

The acetylation state of core histones is controlled by two classes of enzymes, histone acetyl transferases (HATs) and histone deacetylases (HDACs). HDAC inhibitors, such as trichostatin-A (TSA), are able to induce cell cycle arrest by stimulating transcription of genes that negatively regulate cell growth and survival. However, little is known about the effect of HDAC inhibitors on spermatogenesis. TSA treatment of cultured murine germ cells from whole testes resulted in an increase of histone H4 acetylation in round spermatids, suggesting that a hypoacetylated state of these cells is important for their normal differentiation. In the present study, the in vivo effects of TSA on murine spermatogenesis were investigated. Subcutaneously applied TSA resulted in a dose-dependent decrease in relative testis weight due to impaired spermatogenesis. No obvious toxic effects of TSA treatment could be found. A second animal experiment confirmed that male mice receiving TSA under the same conditions as in the first experiment became infertile. This phenomenon was completely reversible. No evidence of histone H4 hyperacetylation in round spermatids could be found; however, the number of spermatids significantly decreased with increasing TSA concentrations. Additionally, a dramatic loss of pachytene-diplotene spermatocytes due to increased apoptosis was observed. This suggests that TSA was mainly effective at the level of meiosis. The other male reproductive organs showed no morphological changes compared to controls, suggesting that TSA action on the testis was not mediated by sex hormones.

     Key words: Histone, mouse, protamine, spermatogenesis

This article has been cited by other articles:

				A. M. Sargeant, R. C. Rengel, S. K. Kulp, R. D. Klein, S. K. Clinton, Y.-C. Wang, and C.-S. Chen OSU-HDAC42, a Histone Deacetylase Inhibitor, Blocks Prostate Tumor Progression in the Transgenic Adenocarcinoma of the Mouse Prostate Model Cancer Res., May 15, 2008; 68(10): 3999 - 4009. [Abstract] [Full Text] [PDF]

				M. G. Wade, A. Kawata, A. Williams, and C. Yauk Methoxyacetic Acid-Induced Spermatocyte Death Is Associated with Histone Hyperacetylation in Rats Biol Reprod, May 1, 2008; 78(5): 822 - 831. [Abstract] [Full Text] [PDF]

				I. Fenic, H. M. Hossain, V. Sonnack, S. Tchatalbachev, F. Thierer, J. Trapp, K. Failing, K. S. Edler, M. Bergmann, M. Jung, et al. In Vivo Application of Histone Deacetylase Inhibitor Trichostatin-A Impairs Murine Male Meiosis J Androl, March 1, 2008; 29(2): 172 - 185. [Abstract] [Full Text] [PDF]

				K. Biermann and K. Steger Epigenetics in Male Germ Cells J Androl, July 1, 2007; 28(4): 466 - 480. [Full Text] [PDF]

				D. T. Carrell, B. R. Emery, and S. Hammoud Altered protamine expression and diminished spermatogenesis: what is the link? Hum. Reprod. Update, May 1, 2007; 13(3): 313 - 327. [Abstract] [Full Text] [PDF]

				S. K. Kulp, C.-S. Chen, D.-S. Wang, C.-Y. Chen, and C.-S. Chen Antitumor Effects of a Novel Phenylbutyrate-Based Histone Deacetylase Inhibitor, (S)-HDAC-42, in Prostate Cancer Clin. Cancer Res., September 1, 2006; 12(17): 5199 - 5206. [Abstract] [Full Text] [PDF]

				J.-S. KIM and S. D. SHUKLA ACUTE IN VIVO EFFECT OF ETHANOL (BINGE DRINKING) ON HISTONE H3 MODIFICATIONS IN RAT TISSUES Alcohol Alcohol., March 1, 2006; 41(2): 126 - 132. [Abstract] [Full Text] [PDF]

				R.-M. Laberge and G. Boissonneault On the Nature and Origin of DNA Strand Breaks in Elongating Spermatids Biol Reprod, August 1, 2005; 73(2): 289 - 296. [Abstract] [Full Text] [PDF]