Hostname: page-component-78c5997874-lj6df Total loading time: 0 Render date: 2024-11-10T09:21:14.910Z Has data issue: false hasContentIssue false
  • English
  • Français

Dynamic reprogramming and function of RNA N6-methyladenosine modification during porcine early embryonic development

Published online by Cambridge University Press:  23 April 2021

Tong Yu ,
Xin Qi ,
Ling Zhang ,
Wei Ning ,
Di Gao ,
Tengteng Xu ,
Yangyang Ma ,
Jason G Knott ,
Anucha Sathanawongs  and
Zubing Cao Open the ORCID record for Zubing Cao [Opens in a new window]
...Show all authors
Tong Yu
Affiliation:
Anhui Province Key Laboratory of Local Livestock and Poultry, Genetical Resource Conservation and Breeding, College of Animal Science and Technology, Anhui Agricultural University, Hefei 230036, China
Xin Qi
Affiliation:
Anhui Province Key Laboratory of Local Livestock and Poultry, Genetical Resource Conservation and Breeding, College of Animal Science and Technology, Anhui Agricultural University, Hefei 230036, China
Ling Zhang
Affiliation:
Anhui Province Key Laboratory of Local Livestock and Poultry, Genetical Resource Conservation and Breeding, College of Animal Science and Technology, Anhui Agricultural University, Hefei 230036, China
Wei Ning
Affiliation:
Anhui Province Key Laboratory of Local Livestock and Poultry, Genetical Resource Conservation and Breeding, College of Animal Science and Technology, Anhui Agricultural University, Hefei 230036, China
Di Gao
Affiliation:
Anhui Province Key Laboratory of Local Livestock and Poultry, Genetical Resource Conservation and Breeding, College of Animal Science and Technology, Anhui Agricultural University, Hefei 230036, China
Tengteng Xu
Affiliation:
Anhui Province Key Laboratory of Local Livestock and Poultry, Genetical Resource Conservation and Breeding, College of Animal Science and Technology, Anhui Agricultural University, Hefei 230036, China
Yangyang Ma
Affiliation:
Anhui Province Key Laboratory of Local Livestock and Poultry, Genetical Resource Conservation and Breeding, College of Animal Science and Technology, Anhui Agricultural University, Hefei 230036, China
Jason G Knott
Affiliation:
Developmental Epigenetics Laboratory, Department of Animal Science, Michigan State University, East Lansing, MI48824, USA
Anucha Sathanawongs
Affiliation:
Department of Veterinary Biosciences and Veterinary Public Health, Faculty of Veterinary Medicine, Chiang Mai University, A. Muang 50100, Thailand
Zubing Cao*
Affiliation:
Anhui Province Key Laboratory of Local Livestock and Poultry, Genetical Resource Conservation and Breeding, College of Animal Science and Technology, Anhui Agricultural University, Hefei 230036, China
Yunhai Zhang*
Affiliation:
Anhui Province Key Laboratory of Local Livestock and Poultry, Genetical Resource Conservation and Breeding, College of Animal Science and Technology, Anhui Agricultural University, Hefei 230036, China
*
Authors for correspondence: Yunhai Zhang and Zubing Cao. College of Animal Science and Technology, Anhui Agricultural University, Hefei230036, China. E-mail: yunhaizhang@ahau.edu.cn; zubingcao@ahau.edu.cn
Authors for correspondence: Yunhai Zhang and Zubing Cao. College of Animal Science and Technology, Anhui Agricultural University, Hefei230036, China. E-mail: yunhaizhang@ahau.edu.cn; zubingcao@ahau.edu.cn
Get access Rights & Permissions [Opens in a new window]

Summary

N6-Methyladenosine (m6A) regulates oocyte-to-embryo transition and the reprogramming of somatic cells into induced pluripotent stem cells. However, the role of m6A methylation in porcine early embryonic development and its reprogramming characteristics in somatic cell nuclear transfer (SCNT) embryos are yet to be known. Here, we showed that m6A methylation was essential for normal early embryonic development and its aberrant reprogramming in SCNT embryos. We identified a persistent occurrence of m6A methylation in embryos between 1-cell to blastocyst stages and m6A levels abruptly increased during the morula-to-blastocyst transition. Cycloleucine (methylation inhibitor, 20 mM) treatment efficiently reduced m6A levels, significantly decreased the rates of 4-cell embryos and blastocysts, and disrupted normal lineage allocation. Moreover, cycloleucine treatment also led to higher levels in both apoptosis and autophagy in blastocysts. Furthermore, m6A levels in SCNT embryos at the 4-cell and 8-cell stages were significantly lower than that in parthenogenetic activation (PA) embryos, suggesting an abnormal reprogramming of m6A methylation in SCNT embryos. Correspondingly, expression levels of m6A writers (METTL3 and METTL14) and eraser (FTO) were apparently higher in SCNT 8-cell embryos compared with their PA counterparts. Taken together, these results indicated that aberrant nuclear transfer-mediated reprogramming of m6A methylation was involved in regulating porcine early embryonic development.

Keywords

Early embryosm6ANuclear transferPigReprogramming
Type
Research Article
Information
Zygote , Volume 29 , Issue 6 , December 2021 , pp. 417 - 426
Copyright
© The Author(s), 2021. Published by Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Footnotes

*

These authors contributed equally to this study.

References

Canovas, S and Ross, PJ (2016). Epigenetics in preimplantation mammalian development. Theriogenology 86, 69–79.CrossRefGoogle ScholarPubMed
Chen, T, Hao, YJ, Zhang, Y, Li, MM, Wang, M, Han, W, Wu, Y, Lv, Y, Hao, J, Wang, L, Li, A, Yang, Y, Jin, KX, Zhao, X, Li, Y, Ping, XL, Lai, WY, Wu, LG, Jiang, G, Wang, HL, Sang, L, Wang, XJ, Yang, YG and Zhou, Q (2015). m6A RNA methylation is regulated by microRNAs and promotes reprogramming to pluripotency. Cell Stem Cell 16, 289–301.CrossRefGoogle Scholar
Cheng, H, Zhang, J, Zhang, S, Zhai, Y, Jiang, Y, An, X, Ma, X, Zhang, X, Li, Z and Tang, B (2019). Tet3 is required for normal in vitro fertilization preimplantation embryos development of bovine. Mol Reprod Dev 86, 298–307.CrossRefGoogle ScholarPubMed
Choi, I, Carey, TS, Wilson, CA and Knott, JG (2012). Transcription factor AP-2gamma is a core regulator of tight junction biogenesis and cavity formation during mouse early embryogenesis. Development 139, 4623–32.CrossRefGoogle ScholarPubMed
Fowler, KE, Mandawala, AA, Griffin, DK, Walling, GA and Harvey, SC (2018). The production of pig preimplantation embryos in vitro: current progress and future prospects. Reprod Biol 18, 203–11.CrossRefGoogle ScholarPubMed
Fraser, R and Lin, CJ (2016). Epigenetic reprogramming of the zygote in mice and men: on your marks, get set, go! Reproduction 152, R211–22.CrossRefGoogle ScholarPubMed
Guo, M, Liu, X, Zheng, X, Huang, Y and Chen, X (2017). m6A RNA modification determines cell fate by regulating mRNA degradation. Cell Reprogram 19, 225–31.CrossRefGoogle ScholarPubMed
Hu, Y, Ouyang, Z, Sui, X, Qi, M, Li, M, He, Y, Cao, Y, Cao, Q, Lu, Q, Zhou, S, Liu, L, Shen, B, Shu, W and Huo, R (2020). Oocyte competence is maintained by m6A methyltransferase KIAA1429-mediated RNA metabolism during mouse follicular development. Cell Death Differ 27, 2468–83.CrossRefGoogle ScholarPubMed
Huang, H, Weng, H and Chen, J (2020). The biogenesis and precise control of RNA m6A methylation. Trends Genet 36, 44–52.CrossRefGoogle ScholarPubMed
Huang, J, Zhang, H, Wang, X, Dobbs, KB, Yao, J, Qin, G, Whitworth, K, Walters, EM, Prather, RS and Zhao, J (2015). Impairment of preimplantation porcine embryo development by histone demethylase KDM5B knockdown through disturbance of bivalent H3K4me3-H3K27me3 modifications. Biol Reprod 92, 72.CrossRefGoogle ScholarPubMed
Ireland, JJ, Roberts, RM, Palmer, GH, Bauman, DE and Bazer, FW (2008). A commentary on domestic animals as dual-purpose models that benefit agricultural and biomedical research. J Anim Sci 86, 2797–805.CrossRefGoogle ScholarPubMed
Kim, MG, Kim, DH, Lee, HR, Lee, JS, Jin, SJ and Lee, HT (2017). Sirtuin inhibition leads to autophagy and apoptosis in porcine preimplantation blastocysts. Biochem Biophys Res Commun 488, 603–8.CrossRefGoogle ScholarPubMed
Kwon, J, Jo, YJ, Namgoong, S and Kim, NH (2019). Functional roles of hnRNPA2/B1 regulated by METTL3 in mammalian embryonic development. Sci Rep 9, 8640.CrossRefGoogle ScholarPubMed
Lee, K, Hamm, J, Whitworth, K, Spate, L, Park, KW, Murphy, CN and Prather, RS (2014). Dynamics of TET family expression in porcine preimplantation embryos is related to zygotic genome activation and required for the maintenance of NANOG. Dev Biol 386, 86–95.CrossRefGoogle ScholarPubMed
Lee, SE, Hwang, KC, Sun, SC, Xu, YN and Kim, NH (2011). Modulation of autophagy influences development and apoptosis in mouse embryos developing in vitro . Mol Reprod Dev 78, 498–509.CrossRefGoogle ScholarPubMed
Lin, T, Lee, JE, Oqani, RK, Kim, SY, Cho, ES, Jeong, YD, Baek, JJ and Jin, DI (2017a). Delayed blastocyst formation or an extra day culture increases apoptosis in pig blastocysts. Anim Reprod Sci 185, 128–39.CrossRefGoogle ScholarPubMed
Lin, Z, Hsu, PJ, Xing, X, Fang, J, Lu, Z, Zou, Q, Zhang, KJ, Zhang, X, Zhou, Y, Zhang, T, Zhang, Y, Song, W, Jia, G, Yang, X, He, C and Tong, MH (2017b). Mettl3-/Mettl14-mediated mRNA N6-methyladenosine modulates murine spermatogenesis. Cell Res 27, 1216–30.CrossRefGoogle ScholarPubMed
Marcho, C, Cui, W and Mager, J (2015). Epigenetic dynamics during preimplantation development. Reproduction 150, R109–20.CrossRefGoogle ScholarPubMed
Matoba, S and Zhang, Y (2018). Somatic cell nuclear transfer reprogramming: mechanisms and applications. Cell Stem Cell 23, 471–85.CrossRefGoogle ScholarPubMed
Nachtergaele, S and He, C (2018). Chemical modifications in the life of an mRNA transcript. Ann Rev Genet 52, 349–72.CrossRefGoogle ScholarPubMed
Park, CH and Hong, K (2017). Epitranscriptome: m6A and its function in stem cell biology. Genes Genome 39, 371–8.CrossRefGoogle Scholar
Perleberg, C, Kind, A and Schnieke, A (2018). Genetically engineered pigs as models for human disease. Dis Model Mech 11, dmm030783.CrossRefGoogle Scholar
Posfai, E, Rovic, I and Jurisicova, A (2019). The mammalian embryo’s first agenda: making trophectoderm. Int J Dev Biol 63, 157–70.CrossRefGoogle ScholarPubMed
Ramos-Ibeas, P, Nichols, J and Alberio, R (2018). States and origins of mammalian embryonic pluripotency in vivo and in a dish. Curr Top Dev Biol 128, 151–79.CrossRefGoogle ScholarPubMed
Shi, H, Wei, J and He, C (2019). Where, when, and how: context-dependent functions of RNA methylation writers, readers, and erasers. Mol Cell 74, 640–50.CrossRefGoogle ScholarPubMed
Shi, W and Haaf, T (2002). Aberrant methylation patterns at the two-cell stage as an indicator of early developmental failure. Mol Reprod Dev 63, 329–34.CrossRefGoogle Scholar
Song, BS, Kim, JS, Kim, YH, Sim, BW, Yoon, SB, Cha, JJ, Choi, SA, Yang, HJ, Mun, SE, Park, YH, Jeong, KJ, Huh, JW, Lee, SR, Kim, SH, Kim, SU and Chang, KT (2014). Induction of autophagy during in vitro maturation improves the nuclear and cytoplasmic maturation of porcine oocytes. Reprod Fertil Dev 26, 974–81.CrossRefGoogle ScholarPubMed
Wang, X, Qu, J, Li, J, He, H, Liu, Z and Huan, Y (2020). Epigenetic reprogramming during somatic cell nuclear transfer: recent progress and future directions. Front Genet 11, 205.CrossRefGoogle ScholarPubMed
Wang, Y, Li, Y, Toth, JI, Petroski, MD, Zhang, Z and Zhao, JC (2014). N6-methyladenosine modification destabilizes developmental regulators in embryonic stem cells. Nat Cell Biol 16, 191–8.CrossRefGoogle ScholarPubMed
Wang, YK, Yu, XX, Liu, YH, Li, X, Liu, XM, Wang, PC, Liu, S, Miao, JK, Du, ZQ and Yang, CX (2018). Reduced nucleic acid methylation impairs meiotic maturation and developmental potency of pig oocytes. Theriogenology 121, 160–7.CrossRefGoogle ScholarPubMed
Wu, R, Liu, Y, Zhao, Y, Bi, Z, Yao, Y, Liu, Q, Wang, F, Wang, Y and Wang, X (2019). m6A methylation controls pluripotency of porcine induced pluripotent stem cells by targeting SOCS3/JAK2/STAT3 pathway in a YTHDF1/YTHDF2-orchestrated manner. Cell Death Dis 10, 171.CrossRefGoogle Scholar
Xia, H, Zhong, C, Wu, X, Chen, J, Tao, B, Xia, X, Shi, M, Zhu, Z, Trudeau, VL and Hu, W (2018). Mettl3 Mutation disrupts gamete maturation and reduces fertility in zebrafish. Genetics 208, 729–43.CrossRefGoogle ScholarPubMed
Xu, Q and Xie, W (2018). Epigenome in Early mammalian development: inheritance, reprogramming and establishment. Trends Cell Biol 28, 237–53.CrossRefGoogle ScholarPubMed
Yang, XQ, Wu, ZF and Li, ZC (2019). Advances in epigenetic reprogramming of somatic cells nuclear transfer in mammals. Yi Chuan 41, 1099–109.Google ScholarPubMed
Yartseva, V and Giraldez, AJ (2015). The maternal-to-zygotic transition during vertebrate development: a model for reprogramming. Curr Top Dev Biol 113, 191–232.CrossRefGoogle Scholar
Zhao, BS, Wang, X, Beadell, AV, Lu, Z, Shi, H, Kuuspalu, A, Ho, RK and He, C (2017). m6A-dependent maternal mRNA clearance facilitates zebrafish maternal-to-zygotic transition. Nature 542, 475–78.CrossRefGoogle ScholarPubMed
Zhou, W, Niu, YJ, Nie, ZW, Kim, JY, Xu, YN, Yan, CG and Cui, XS (2020). Nuclear accumulation of pyruvate dehydrogenase alpha 1 promotes histone acetylation and is essential for zygotic genome activation in porcine embryos. Biochim Biophys Acta Mol Cell Res 1867, 118648.CrossRefGoogle ScholarPubMed
Supplementary material: File

Yu et al. supplementary material

Figure S1

Download Yu et al. supplementary material(File)
File 91.9 KB