Journal of Andrology
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Published-Ahead-of-Print November 28, 2007, DOI:10.2164/jandrol.107.003848

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In-Vivo Application of Histone Deacetylase Inhibitor Trichostatin-A Impairs Murine Male Meiosis

Irina Fenic , Hamid M. Hossain , Violetta Sonnack , Svetlin Tchatalbachev , Felix Thierer , Johannes Trapp , Klaus Failing , Kai S. Edler , Martin Bergmann , Manfred Jung , Trinad Chakraborty , and Klaus Steger *

* To whom correspondence should be addressed. E-mail: klaus.steger{at}chiru.med.uni-giessen.de.

In-vivo application of histone deacetylase (HDAC) inhibitor trichostatin-A (TSA) in mice results in male infertility. To get more insight into the mechanisms underlying this phenomenon, we performed a gene expression analysis and investigated HDAC activity and degree of histone H3 and H4 acetylation in murine testes after TSA treatment. A significant decrease of HDAC activity and a weak increase of histone acetylation could be demonstrated at 2.5, 5.0 and 7.5 hours after TSA application. Gene expression analysis revealed 507 significantly regulated genes. Transcripts expressed in the somatic cells of the testis (Sertoli, Leydig, peritubular cells, testis macrophages) or extratubular matrix were regulated as early as 2.5 hours after TSA application, whereas very few meiosis-specific genes were modulated after TSA treatment. In addition, members of the p53-noxa-caspase-3 proapoptotic pathway were early regulated. Applying in-situ hybridization, caspase-3-mRNA was found only in apoptotic spermatocytes, while TRP53/p53- and pmaip1/noxa-mRNA could be demonstrated in spermatogonia and spermatocytes. Our data suggest that TSA impaired male meiosis possibly through an indirect mechanism implicating somatic cells of the testis.


Key words: Infertility • Spermatogenesis • Testis






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