Genome wide abnormal DNA methylome of human blastocyst in assisted reproductive technology

Guoqiang Li^{a, b, #},
Yang Yu^{a, #},
Yong Fan^{c, #},
Congru Li^{b, d, #},
Xiaocui Xu^{b, d},
Jialei Duan^b,
Rong Li^a,
Xiangjin Kang^c,
Xin Ma^{b, d},
Xuepeng Chen^{b, d},
Yuwen Ke^b,
Jie Yan^a,
Ying Lian^a,
Ping Liu^a,
Yue Zhao^a,
Hongcui Zhao^a,
Yaoyong Chen^c,
Xiaofang Sun^c,
Jianqiao Liu^c,
Jie Qiao^{a
, ,},
Jiang Liu^{b, d
, ,}

a.
Ministry of Education Key Laboratory of Assisted Reproduction, Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Center of Reproductive Medicine, Peking University Third Hospital, Beijing 100191, China
b.
CAS Key Laboratory of Genome Sciences and Information, Collaborative Innovation Center of Genetics and Development, Beijing Institute of Genomics, CAS, Beijing 100101, China
c.
Key Laboratory for Major Obstetric Diseases of Guangdong Province, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, China
d.
University of Chinese Academy of Sciences, Beijing 100029, China

More Information

Corresponding author: E-mail address: jie.qiao@263.net (Jie Qiao); E-mail address: liuj@big.ac.cn (Jiang Liu)

These authors contributed equally to this work.

摘要

- /
- /
- /
- /
Abstract: Proper reprogramming of parental DNA methylomes is essential for mammalian embryonic development. However, it is unknown whether abnormal methylome reprogramming occurs and is associated with the failure of embryonic development. Here we analyzed the DNA methylomes of 57 blastocysts and 29 trophectoderm samples with different morphological grades during assisted reproductive technology (ART) practices. Our data reveal that the global methylation levels of high-quality blastocysts are similar (0.30 ± 0.02, mean ± SD), while the methylation levels of low-quality blastocysts are divergent and away from those of high-quality blastocysts. The proportion of blastocysts with a methylation level falling within the range of 0.30 ± 0.02 in different grades correlates with the live birth rate for that grade. Moreover, abnormal methylated regions are associated with the failure of embryonic development. Furthermore, we can use the methylation data of cells biopsied from trophectoderm to predict the blastocyst methylation level as well as to detect the aneuploidy of the blastocysts. Our data indicate that global abnormal methylome reprogramming often occurs in human embryos, and suggest that DNA methylome is a potential biomarker in blastocyst selection in ART.
- Human /
- Abnormal /
- Blastocyst /
- Methylome /
- ART
These authors contributed equally to this work.
注释:

HTML全文

参考文献(46)

[1]	Akalin, A., Kormaksson, M., Li, S. et al. methylKit: a comprehensive R package for the analysis of genome-wide DNA methylation profiles Genome Biol., 13 (2012),pp. 1-9
[2]	Anders, S., Huber, W. Differential expression analysis for sequence count data Genome Biol., 11 (2010),pp. 1-12
[3]	Baubec, T., Colombo, D.F., Wirbelauer, C. et al. Genomic profiling of DNA methyltransferases reveals a role for DNMT3B in genic methylation Nature, 520 (2015),pp. 243-247
[4]	Baylin, S.B., Jones, P.A. A decade of exploring the cancer epigenome - biological and translational implications Nat. Rev. Cancer, 11 (2011),pp. 726-734
[5]	Bolger, A.M., Lohse, M., Usadel, B. Trimmomatic: a flexible trimmer for Illumina sequence data Bioinformatics, 30 (2014),pp. 2114-2120
[6]	Centers for Disease Control and Prevention, American Society for Reproductive Medicine, Society for Assisted Reproductive Technology
[7]	Dahdouh, E.M., Balayla, J., Audibert, F. et al. Technical update: preimplantation genetic diagnosis and screening J. Obstet. Gynaecol. Can., 37 (2015),pp. 451-463
[8]	Evers, J.L. Female subfertility Lancet, 360 (2002),pp. 151-159
[9]	Feber, A., Guilhamon, P., Lechner, M. et al. Using high-density DNA methylation arrays to profile copy number alterations Genome Biol., 15 (2014),pp. 1-13
[10]	Fiorentino, F., Biricik, A., Bono, S. et al. Development and validation of a next-generation sequencing based protocol for 24-chromosome aneuploidy screening of embryos Fertil. Steril., 101 (2014),pp. 1375-1382
[11]	Forman, E.J., Hong, K.H., Ferry, K.M. et al. Fertil. Steril., 100 (2013),pp. 100-107
[12]	Fragouli, E., Alfarawati, S., Daphnis, D.D. et al. Cytogenetic analysis of human blastocysts with the use of FISH, CGH and aCGH: scientific data and technical evaluation Hum. Reprod., 26 (2011),pp. 480-490
[13]	Franasiak, J.M., Forman, E.J., Hong, K.H. et al. Aneuploidy across individual chromosomes at the embryonic level in trophectoderm biopsies: changes with patient age and chromosome structure J. Assist. Reprod. Genet., 31 (2014),pp. 1501-1509
[14]	Franasiak, J.M., Forman, E.J., Hong, K.H. et al. The nature of aneuploidy with increasing age of the female partner: a review of 15,169 consecutive trophectoderm biopsies evaluated with comprehensive chromosomal screening Fertil. Steril., 101 (2014),pp. 656-663
[15]	Gu, T.P., Guo, F., Yang, H. et al. The role of Tet3 DNA dioxygenase in epigenetic reprogramming by oocytes Nature, 477 (2011),pp. 606-610
[16]	Guo, H., Zhu, P., Yan, L. et al. The DNA methylation landscape of human early embryos Nature, 511 (2014),pp. 606-610
[17]	Ha, G., Roth, A., Lai, D. et al. Integrative analysis of genome-wide loss of heterozygosity and monoallelic expression at nucleotide resolution reveals disrupted pathways in triple-negative breast cancer Genome Res., 22 (2012),pp. 1995-2007
[18]	Handyside, A.H., Lesko, J.G., Tarin, J.J. et al. New Engl. J. Med., 327 (1992),pp. 905-909
[19]	Hansen, K.D., Timp, W., Bravo, H.C. et al. Increased methylation variation in epigenetic domains across cancer types Nat. Genet., 43 (2011),pp. 768-775
[20]	Hansen, K.D., Langmead, B., Irizarry, R.A. BSmooth: from whole genome bisulfite sequencing reads to differentially methylated regions Genome Biol., 13 (2012),pp. 1-10
[21]	Hardarson, T., Van Landuyt, L., Jones, G. The blastocyst Hum. Reprod., 27 (2012),pp. 72-91
[22]	Heitmann, R.J., Hill, M.J., Richter, K.S. et al. The simplified SART embryo scoring system is highly correlated to implantation and live birth in single blastocyst transfers J. Assist. Reprod. Genet., 30 (2013),pp. 563-567
[23]	Hill, M.J., Richter, K.S., Heitmann, R.J. et al. Trophectoderm grade predicts outcomes of single-blastocyst transfers Fertil. Steril., 99 (2013),pp. 1283-1289
[24]	Jiang, L., Zhang, J., Wang, J.-J. et al. Sperm, but not oocyte, DNA methylome is inherited by zebrafish early embryos Cell, 153 (2013),pp. 773-784
[25]	Jirtle, R.L., Skinner, M.K. Environmental epigenomics and disease susceptibility Nat. Rev. Genet., 8 (2007),pp. 253-262
[26]	, McKnight, S.L. Influence of metabolism on epigenetics and disease Cell, 153 (2013),pp. 56-69
[27]	Krueger, F., Andrews, S.R. Bismark: a flexible aligner and methylation caller for Bisulfite-Seq applications Bioinformatics, 27 (2011),pp. 1571-1572
[28]	Lee, H.J., Lowdon, R.F., Maricque, B. et al. Developmental enhancers revealed by extensive DNA methylome maps of zebrafish early embryos Nat. Commun., 6 (2015),p. 6315
[29]	Lehnen, H., Zechner, U., Haaf, T. Epigenetics of gestational diabetes mellitus and offspring health: the time for action is in early stages of life Mol. Hum. Reprod., 19 (2013),pp. 415-422
[30]	Li, E., Bestor, T.H., Jaenisch, R. Targeted mutation of the DNA methyltransferase gene results in embryonic lethality Cell, 69 (1992),pp. 915-926
[31]	Li, H., Handsaker, B., Wysoker, A. et al. The sequence alignment/map format and SAMtools Bioinformatics, 25 (2009),pp. 2078-2079
[32]	Macklon, N.S., Geraedts, J.P., Fauser, B.C. Conception to ongoing pregnancy: the 'black box' of early pregnancy loss Hum. Reprod. Update, 8 (2002),pp. 333-343
[33]	National Collaborating Centre for Women's and Children's Health (UK)
[34]	Oda, M., Glass, J.L., Thompson, R.F. et al. High-resolution genome-wide cytosine methylation profiling with simultaneous copy number analysis and optimization for limited cell numbers Nucleic Acids Res., 37 (2009),pp. 3829-3839
[35]	Okano, M., Bell, D.W., Haber, D.A. et al. Cell, 99 (1999),pp. 247-257
[36]	Pujadas, E., Feinberg, A.P. Regulated noise in the epigenetic landscape of development and disease Cell, 148 (2012),pp. 1123-1131
[37]	Schubeler, D. Function and information content of DNA methylation Nature, 517 (2015),pp. 321-326
[38]	, Upham, K.M., Forman, E.J., Hong, K.H. et al. Fertil. Steril., 100 (2013),pp. 697-703
[39]	Shen, H., Laird, P.W. Interplay between the cancer genome and epigenome Cell, 153 (2013),pp. 38-55
[40]	Smith, Z.D., Chan, M.M., Mikkelsen, T.S. et al. A unique regulatory phase of DNA methylation in the early mammalian embryo Nature, 484 (2012),pp. 339-344
[41]	Smith, Z.D., Chan, M.M., Humm, K.C. et al. DNA methylation dynamics of the human preimplantation embryo Nature, 511 (2014),pp. 611-615
[42]	Snedecor, G.W., Cochran, W.G.
[43]	Tee, L., Lim, D.H.K., Dias, R.P. et al. Epimutation profiling in Beckwith-Wiedemann syndrome: relationship with assisted reproductive technology Clin. Epigenetics, 5 (2013)
[44]	Trapnell, C., Pachter, L., Salzberg, S.L. TopHat: discovering splice junctions with RNA-Seq Bioinformatics, 25 (2009),pp. 1105-1111
[45]	Wang, L., Zhang, J., Duan, J. et al. Programming and inheritance of parental DNA methylomes in mammals Cell, 157 (2014),pp. 979-991
[46]	Wells, D., Delhanty, J.D. Preimplantation genetic diagnosis: applications for molecular medicine Trends Mol. Med., 7 (2001),pp. 23-30

施引文献

资源附件(0)

访问统计

点击查看大图

计量

文章访问数: 119
HTML全文浏览量: 60
PDF下载量: 9
被引次数: 0

姓名
邮箱
手机号码
标题
留言内容
验证码

留言板

doi: 10.1016/j.jgg.2017.09.001

计量

Genome wide abnormal DNA methylome of human blastocyst in assisted reproductive technology

Corresponding author: E-mail address: jie.qiao@263.net (Jie Qiao); E-mail address: liuj@big.ac.cn (Jiang Liu)

计量

目录

留言板

doi: 10.1016/j.jgg.2017.09.001

计量

出版历程

Genome wide abnormal DNA methylome of human blastocyst in assisted reproductive technology

Corresponding author: E-mail address: jie.qiao@263.net (Jie Qiao); E-mail address: liuj@big.ac.cn (Jiang Liu)

计量

出版历程

目录