The Histone Deacetylase Inhibitor Trichostatin A Induces Retrogressive Chromatin Decondensation in the Germinal Vesicle of Porcine Cumulus-enclosed Oocytes

Abstract

In porcine growing oocytes, chromatin remains diffuse. As the oocytes approach their final size, 120 μm, the chromatin becomes partly condensed and forms a perinucleolar sheath. These changes occur simultaneously with a decrease in transcriptional activity. In many other cell types, it has been shown that the state of acetylation of nucleosome core histones is essential in chromatin remodeling and transcription so that partial chromatin condensation in oocytes may involve the recruitment of histone deacetylases. In order to test this hypothesis, porcine oocyte-cumulus cell complexes were treated with a specific inhibitor of histone deacetylases, trichostatin A (TSA). The perinucleolar sheath loosened or disappeared after 24 hr culture with 100 nM TSA, but after further culture in TSA-free medium, about 40% developed the perinucleolar sheath again. In the presence of 4 mM hypoxanthine, the decondensation induced by TSA progressed rather slowly, but continuously, for 72 hr. When oocytes were denuded before culture, spontaneous maturation occurred in the presence of TSA. Thus, the inhibitor-induced decondensation is not attributed to the inhibition of the maturation-promoting factor. These results suggest that deacetylation of histones may be involved in chromatin remodeling in oocytes near the end of the growth phase.