HDAC inhibition decreases XIST expression on female IVP bovine blastocysts

Autor(es)

Oliveira, Clara Slade ^{[1, 2]} ; Saraiva, Naiara Zoccal ^[1] ; Coelho Cruz, Maria Helena ^[1] ; Mazeti, Bruna ^[1] ; Oliveira, Leticia Zoccolaro ^[1] ; Lopes, Flavia Lombardi ^[1] ; Garcia, Joaquim Mansano ^[1]

Afiliação do(s) autor(es)

^[1] Univ Estadual Paulista, Dept Med Vet Prevent & Reprod Anim, Jaboticabal - Brazil

^[2] Embrapa Dairy Cattle Res Ctr, Juiz De Fora - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Reproduction; v. 145, n. 1, p. 9-17, JAN 2013.
• Citações Web of Science: 13

Resumo

During initial development, both X chromosomes are active in females, and one of them must be silenced at the appropriate time in order to dosage compensate their gene expression levels to male counterparts. Silencing involves epigenetic mechanisms, including histone deacetylation. Major X chromosome inactivation (XCI) in bovine occurs between hatching and implantation, although in vitro culture conditions might disrupt the silencing process, increasing or decreasing X-linked gene expression. In this study, we aimed to address the roles of histone deacetylase inhibition by trichostatin A (TSA) on female preimplantation development. We tested the hypothesis that by enhancing histone acetylation, TSA would increase the percentage of embryos achieving 16-cell stage, reducing percentage of embryos blocked at 8-cell stage, and interfere with XCI in IVF embryos. We noticed that after TSA treatment, acetylation levels in individual blastomeres of 8-16 cell embryos were increased twofold on treated embryos, and the same was detected for blastocysts. Changes among blastomere levels within the same embryo were diminished on TSA group, as low-acetylated blastomeres were no longer detected. The percentage of embryos that reached the 5th cleavage cycle 118 h after IVF, analyzed by Hoechst staining, remained unaltered after TSA treatment. Then, we assessed XIST and G6PD expression in individual female bovine blastocysts by quantitative real-time PCR. Even though G6PD expression remained unaltered after TSA exposure, XIST expression was eightfold decreased, and we also detected a major decrease in the percentage of blastocysts expressing detectable XIST levels after TSA treatment. Based on these results, we conclude that HDAC is involved on XCI process in bovine embryos, and its inhibition might delay X chromosome silencing and attenuate aberrant XIST expression described for IVF embryos. Reproduction (2013) 145 9-17 (AU)

• Processo FAPESP: 08/58370-0 - Comparação do perfil epigenético de genes relacionados à diferenciação neural murina em tipos celulares obtidos a partir de células tronco embrionárias diferenciadas in vitro e in vivo e de células de massa interna de embriões
• Beneficiário: Clara Slade Oliveira
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 09/54510-4 - Comparação do perfil epigenético de genes relacionados a diferenciação neural murina em tipos celulares obtidos a partir de células tronco embrionárias diferenciadas in vitro e in vivo de células da massa celular interna de embriões
• Beneficiário: Joaquim Mansano Garcia
• Modalidade de apoio: Auxílio à Pesquisa - Regular