Effects of trichostatin A, a histone deacetylase inhibitor, on mouse gonadal development in vitro

• Published in: Journal of Reproduction and Development Vol. 50; no. 2; pp. 227 - 235
• Main Authors: Mizukami, T. (Tokyo Univ. (Japan)), Fujisawa, M, Kanai, Y, Kurohmaru, M, Hayashi, Y
• Format: Journal Article
• Language: English
• Published: Japan THE SOCIETY FOR REPRODUCTION AND DEVELOPMENT 01.04.2004
• Subjects: Animals; Anti-Mullerian Hormone; Apoptosis; Cell Differentiation - drug effects; Cell Division - drug effects; CHROMATIN; Chromatin - metabolism; DNA (Cytosine-5-)-Methyltransferases - biosynthesis; Dose-Response Relationship, Drug; ENZYME INHIBITORS; Enzyme Inhibitors - pharmacology; Female; GAMETES; GENITALIA; Germ cell; Germ Cells - drug effects; Glycoproteins - metabolism; Gonad; Gonads - cytology; Gonads - metabolism; Histone acetylation; Histone Deacetylase Inhibitors; Hydroxamic Acids - pharmacology; IN VITRO EXPERIMENTATION; Male; MICE; Mice, Inbred ICR; Organ Culture Techniques; Reverse Transcriptase Polymerase Chain Reaction; RNA - metabolism; Sertoli Cells - cytology; Sertoli Cells - ultrastructure; Sex determination; SEX DIFFERENTIATION; Sex Factors; Testicular Hormones - metabolism; Testis - drug effects; Testis - metabolism; Testis - ultrastructure; Time Factors; Transcription, Genetic; Trichostatin A
• ISSN: 0916-8818; 1348-4400
• DOI: 10.1262/jrd.50.227

Sry, Sox9 and M33 are thought to act as architectural transcription factors or as a chromatin regulator in gonadal development. However, the direct relationship between chromatin structure and sex determination has not yet been revealed. To clarify the effect of chromatin structural change on gonadal development, we examined the effects of trichostatin A, a histone deacetylase inhibitor, on mouse gonadal development in vitro. In the 0.1 microM treated testicular explants, the size of the gonad was significantly decreased, although the testicular cord formation occurred normally. In the 1.0 microM treated explants, the gonads revealed one or two large testicular cords. Sox9 and MIS expressions suggest that Sertoli cell differentiation is induced normally within the testicular cord, while Dnmt3b expression suggests that several immature Sertoli cells are located on the outside of the testicular cord. The 3v-hsd expression indicates that Leydig cell differentiation occurs normally. On the other hand, germ cell loss was observed in the treated testicular explants. In the treated ovarian explants, the number of premeiotic germ cells was reduced without gonadal size change. Thus, trichostatin A affects the development of germ cells, but does not affect sex determination.