Histone deacetylation inhibitors affect in vitro oocyte maturation and somatic cell nuclear transfer in pigs https://doi.org/10.12982/VIS.2025.078
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Abstract
Histone deacetylase inhibitors (HDACi), such as Trichostatin A (TSA) and Valproic acid (VPA), are known treatment strategies to improve somatic cell nuclear transfer (SCNT) efficiency in various species, including porcine. However, their supportive roles in oocyte maturation and preimplantation embryonic development come with a prolonged meiotic division during in vitro maturation. This study examined the effects of TSA, VPA, and combined TSA and VPA treatments on porcine cumulus-oocyte complexes (COCs), as well as on parthenogenetic activation (PA)- and SCNT-derived embryos. Nuclear maturation of porcine oocytes in vitro was assessed through aceto-orcein staining, while the developmental rates of PA- and SCNT-derived embryos were also observed. Results revealed that TSA treatment significantly inhibited nuclear maturation in porcine oocytes, whereas VPA and TSA+VPA treatments did not differ significantly from the control. There were also no notable differences in blastocyst rates among PA-derived embryos. However, VPA treatment led to a higher blastocyst rate in porcine SCNT embryos. The combination of TSA and VPA appeared to have a synergistic effect on embryo development, with VPA supporting TSA’s effects. Overall, VPA treatment resulted in fewer inhibitory effects on oocyte maturation and improved embryo development more effectively than TSA. These findings contribute to our present understanding of the role of histone deacetylation in porcine oocyte and SCNT-derived embryo development during in vitro production.
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References
Al-Ghadi, M.Q., Alhimaidi, A.R., Iwamoto, D., Al-Mutary, M.G., Ammari, A.A., Saeki, K.O., Aleissa, M.S., 2020. The in vitro development of cloned sheep embryos treated with scriptaid and trichostatin A. Saudi J. Biol. Sci. 27(9), 2280-2286.
Bui, H.T., Wakayama, S., Kishigami, S., Park, K.K., Kim, J.H., Thuan, N.V., Wakayama, T., 2010. Effect of trichostatin A on chromatin remodeling, histone modifications, DNA replication, and transcriptional activity in cloned mouse embryos. Biol. Reprod. 83(3), 454-463.
Chen, X., Wong, J.Y., Wong, P., Radany, E.H., 2011. Low-dose valproic acid enhances radiosensitivity of prostate cancer through acetylated p53-dependent modulation of mitochondrial membrane potential and apoptosis. Mol. Cancer. Res. 9(4), 448-461.
Costa-Borges, N., Santaló, J., Ibáñez, E., 2010. Comparison between the effects of valproic acid and trichostatin A on the in vitro development, blastocyst quality, and full-term development of mouse somatic cell nuclear transfer embryos. Cell. Reprogram. 12(4), 437-446.
Dsilva, P., Pai, P., Shetty, M.G., Babitha, K.S., 2023. The role of histone deacetylases in embryonic development. Mol. Reprod. Dev. 90(1), 14-26.
Endo, T., Kano, K., Naito, K., 2008. Nuclear histone deacetylases are not required for global histone deacetylation during meiotic maturation in porcine oocytes. Biol. Reprod. 78(6), 1073-1080.
Endo, T., Naito, K., Aoki, F., Kume, S., Tojo, H., 2005. Changes in histone modifications during in vitro maturation of porcine oocytes. Mol. Reprod. Dev. 71(1), 123-128.
Endo, T., Naito, K., Kume, S., Nishimura, Y., Kashima, K., Tojo, H., 2006. Activities of maturation-promoting factor (MPF) and mitogen-activated protein kinase (MAPK) are not required for the global histone deacetylation observed after germinal vesicle breakdown (GVBD) in porcine oocytes. Reprod. 131(3), 439-447.
Gao, H., Bai, H., Ao, X., Sa, R., Wang, H., Wang, Z., Yue, Y., Yu, H., 2014. The effect of valproic acid on bovine oocyte maturation and early embryonic development in vitro. Cytotechnology. 66(3), 525-532.
Göttlicher, M., Minucci, S., Zhu, P., Krämer, O.H., Schimpf, A., Giavara, S., Sleeman, J.P., Lo-Coco, F., Nervi, C., Pelicci, P.G., Heinzel, T., 2001. Valproic acid defines a novel class of HDAC inhibitors inducing differentiation of transformed cells. Embo. J. 20(24), 6969-6978.
Huang, Y., Yuan, L., Li, T., Wang, A., Li, Z., Pang, D., Wang, B., Ouyang, H., 2015. Valproic acid improves porcine parthenogenetic embryo development through transient remodeling of histone modifiers. Cell. Physiol. Biochem. 37(4), 1463-1473.
Inoue, K., Oikawa, M., Kamimura, S., Ogonuki, N., Nakamura, T., Nakano, T., Abe, K., Ogura, A., 2015. Trichostatin A specifically improves the aberrant expression of transcription factor genes in embryos produced by somatic cell nuclear transfer. Sci. Rep. 5(1), 10127.
Jeseta, M., Petr, J., Krejcová, T., Chmelíková, E., Jílek, F., 2008. In vitro ageing of pig oocytes: effects of the histone deacetylase inhibitor trichostatin A. Zygote. 16(2), 145-152.
Jin, Y.X., Zhao, M.H., Zheng, Z., Kwon, J.S., Lee, S.K., Cui, X.S., Kim, N.H., 2014. Histone deacetylase inhibitor trichostatin A affects porcine oocyte maturation in vitro. Reprod. Fertil. Dev. 26(6), 806-816.
Kang, J.D., Li, S., Lu, Y., Wang, W., Liang, S., Liu, X., Jin, J.X., Hong, Y., Yan, C.G., Yin, X.J., 2013. Valproic acid improved in vitro development of pig cloning embryos but did not improve survival of cloned pigs to adulthood. Theriogenology. 79(2), 306-311.
Kim, J.M., Liu, H., Tazaki, M., Nagata, M., Aoki, F., 2003. Changes in histone acetylation during mouse oocyte meiosis. J. Cell. Biol. 162(1), 37-46.
Kim, Y.J., Ahn, K.S., Kim, M., Shim, H., 2011. Comparison of potency between histone deacetylase inhibitors trichostatin A and valproic acid on enhancing in vitro development of porcine somatic cell nuclear transfer embryos. In Vitro Cell. Dev. Biol. Anim. 47(4), 283-289.
Lee, M.J., Kim, S.W., Lee, H.G., Im, G.S., Yang, B.C., Kim, N.H., Kim, D.H., 2011. Trichostatin A promotes the development of bovine somatic cell nuclear transfer embryos. J. Reprod. Dev. 57(1), 34-42.
Li, G., Tian, Y., Zhu, W.G., 2020. The roles of histone deacetylases and their inhibitors in cancer therapy. Front. Cell Dev. Biol. 8, 576946.
Luo, B., Ju, S., Muneri, C.W., Rui, R., 2015. Effects of histone acetylation status on the early development of in vitro porcine transgenic cloned embryos. Cell. Reprogram. 17(1), 41-48.
Oh, H.J., Lee, T.H., Lee, J.H., Lee, B.C., 2012. Trichostatin A improves preimplantation development of bovine cloned embryos and alters expression of epigenetic and pluripotency genes in cloned blastocysts. J. Vet. Med. Sci. 74(11), 1409-1415.
Park, S.Y., Kim, J.S., 2020. A short guide to histone deacetylases including recent progress on class II enzymes. Exp. Mol. Med. 52(2), 204-212.
Phung, D., Nguyen, L.H.K., Ho, T.N., Co, A.K.N., Bui, H.T., Van Thuan, N., 2018. Effect of follicular fluid and floating drop culture system on the maturation of bovine oocytes. In: Toi, V.V., Nguyen Le, T.T., Nguyen, D.T. (Eds.), 6th International Conference on the Development of Biomedical Engineering in Vietnam. Springer Nature Singapore, Singapore, pp. 596–600.
Qin, Z.X., Huang, G.B., Luo, J., Ning, S.F., Lu, S.S., Lu, K.H., 2012. Effect of TSA and VPA treatment on long-tailed macaque (Macaca fascicularis)-pig interspecies somatic cell nuclear transfer. Yi Chuan. 34(3), 342-347.
Shi, L.H., Miao, Y.L., Ouyang, Y.C., Huang, J.C., Lei, Z.L., Yang, J.W., Han, Z.M., Song, X.F., Sun, Q.Y., Chen, D.Y., 2008. Trichostatin A (TSA) improves the development of rabbit-rabbit intraspecies cloned embryos, but not rabbit-human interspecies cloned embryos. Dev. Dyn. 237(3), 640-648.
Song, B.S., Yoon, S.B., Sim, B.W., Kim, Y.H., Cha, J.J., Choi, S.A., Jeong, K.J., Kim, J.S., Huh, J.W., Lee, S.R., Kim, S.H., Kim, S.U., Chang, K.T., 2014. Valproic acid enhances early development of bovine somatic cell nuclear transfer embryos by alleviating endoplasmic reticulum stress. Reprod. Fertil. Dev. 26(3), 432-440.
Srirattana, K., Imsoonthornruksa, S., Laowtammathron, C., Sangmalee, A., Tunwattana, W., Thongprapai, T., Chaimongkol, C., Ketudat-Cairns, M., Parnpai, R., 2012. Full-term development of gaur-bovine interspecies somatic cell nuclear transfer embryos: effect of trichostatin A treatment. Cell. Reprogram. 14(3), 248-257.
Srirattana, K., Kaneda, M., Parnpai, R., 2022. Strategies to improve the efficiency of somatic cell nuclear transfer. Int. J. Mol. Sci. 23(4), 1969.
Wang, L., Liu, L., Wang, Y., Li, N., Zhu, H., Chen, M., Bai, J., Pang, Y., Zhang, Y., Zhang, H., 2021. Aberrant epigenetic reprogramming in the first cell cycle of bovine somatic cell nuclear transfer embryos. Cell. Reprogram. 23(2), 99-107.
Wang, Q., Yin, S., Ai, J.S., Liang, C.G., Hou, Y., Chen, D.Y., Schatten, H., Sun, Q.Y., 2006. Histone deacetylation is required for orderly meiosis. Cell Cycle. 5(7), 766-774.
Zhao, J., Hao, Y., Ross, J.W., Spate, L.D., Walters, E.M., Samuel, M.S., Rieke, A., Murphy, C.N., Prather, R.S., 2010. Histone deacetylase inhibitors improve in vitro and in vivo developmental competence of somatic cell nuclear transfer porcine embryos. Cell. Reprogram. 12(1), 75-83.