Semin Reprod Med 2018; 36(03/04): e1-e9
DOI: 10.1055/s-0039-1688801
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Oocyte and Embryo Manipulation and Epigenetics

Emily Osman
1   IVI-Reproductive Medicine Associates of New Jersey, Basking Ridge, New Jersey
2   Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania
,
Jason Franasiak
1   IVI-Reproductive Medicine Associates of New Jersey, Basking Ridge, New Jersey
2   Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania
,
Richard Scott
1   IVI-Reproductive Medicine Associates of New Jersey, Basking Ridge, New Jersey
2   Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania
› Author Affiliations
Further Information

Publication History

Publication Date:
14 May 2019 (online)

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Abstract

Regulation of the epigenome is a mechanism by which the environment influences gene expression and consequently the health of the individual. The advent and refinement of novel assisted reproductive technology (ART) laboratory techniques, including vitrification, dynamic culture systems, oocyte in vitro maturation, laser-assisted hatching, intracytoplasmic sperm injection, and preimplantation genetic testing for aneuploidy have contributed to the success of ART. From fertilization through implantation, the epigenetic profile of the embryo changes dynamically. Concurrently with these changes, embryo development in vitro is dependent on laboratory intervention and manipulation to optimize outcomes. The impact of ART techniques on imprinting errors remains unclear, as the infertile population likely confers an independent risk factor for defects in expected epigenetic patterns. Alternations in epigenetic mechanisms may contribute to the incidence of aneuploidy as well as recurrent implantation failure of euploid embryos. Additional investigative efforts are needed to assess the contribution of oocyte and embryo manipulation on imprinting modifications in this vulnerable population. The development of diagnostic modalities involving the discovery of epigenetic alterations to improve in vitro fertilization outcomes is an exciting and promising area of future study.

Keywords

oocyte - embryo manipulation - epigenetics
 

  • References

  • 1 Centers for Disease Control and Prevention, American Society for Reproductive Medicine, Society for Assisted Reproductive Technology. 2015 Assisted Reproductive Technology National Summary Report. Atlanta (GA): US Department of Health and Human Services; 2017
    Google Scholar
  • 2 Davies MJ, Moore VM, Willson KJ. , et al. Reproductive technologies and the risk of birth defects. N Engl J Med 2012; 366 (19) 1803-1813
    CrossrefPubMedGoogle Scholar
  • 3 Källén B, Finnström O, Nygren KG, Olausson PO. In vitro fertilization (IVF) in Sweden: infant outcome after different IVF fertilization methods. Fertil Steril 2005; 84 (03) 611-617
    CrossrefPubMedGoogle Scholar
  • 4 Lazaraviciute G, Kauser M, Bhattacharya S, Haggarty P, Bhattacharya S. A systematic review and meta-analysis of DNA methylation levels and imprinting disorders in children conceived by IVF/ICSI compared with children conceived spontaneously. Hum Reprod Update 2014; 20 (06) 840-852
    CrossrefPubMedGoogle Scholar
  • 5 Owen CM, Segars Jr JH. Imprinting disorders and assisted reproductive technology. Semin Reprod Med 2009; 27 (05) 417-428
    Article in Thieme ConnectPubMedGoogle Scholar
  • 6 Gosden R, Trasler J, Lucifero D, Faddy M. Rare congenital disorders, imprinted genes, and assisted reproductive technology. Lancet 2003; 361 (9373): 1975-1977
    CrossrefPubMedGoogle Scholar
  • 7 Wolffe AP, Matzke MA. Epigenetics: regulation through repression. Science 1999; 286 (5439): 481-486
    CrossrefPubMedGoogle Scholar
  • 8 Laprise SL. Implications of epigenetics and genomic imprinting in assisted reproductive technologies. Mol Reprod Dev 2009; 76 (11) 1006-1018
    CrossrefPubMedGoogle Scholar
  • 9 Sasaki H, Matsui Y. Epigenetic events in mammalian germ-cell development: reprogramming and beyond. Nat Rev Genet 2008; 9 (02) 129-140
    CrossrefPubMedGoogle Scholar
  • 10 Ma P, Pan H, Montgomery RL, Olson EN, Schultz RM. Compensatory functions of histone deacetylase 1 (HDAC1) and HDAC2 regulate transcription and apoptosis during mouse oocyte development. Proc Natl Acad Sci U S A 2012; 109 (08) E481 –E489
    CrossrefPubMedGoogle Scholar
  • 11 Lawrence LT, Moley KH. Epigenetics and assisted reproductive technologies: human imprinting syndromes. Semin Reprod Med 2008; 26 (02) 143-152
    Article in Thieme ConnectPubMedGoogle Scholar
  • 12 Allegrucci C, Thurston A, Lucas E, Young L. Epigenetics and the germline. Reproduction 2005; 129 (02) 137-149
    CrossrefPubMedGoogle Scholar
  • 13 Lindeman RE, Pelegri F. Vertebrate maternal-effect genes: insights into fertilization, early cleavage divisions, and germ cell determinant localization from studies in the zebrafish. Mol Reprod Dev 2010; 77 (04) 299-313
    CrossrefPubMedGoogle Scholar
  • 14 Reik W, Kelsey G. Epigenetics: cellular memory erased in human embryos. Nature 2014; 511 (7511): 540-541
    PubMedGoogle Scholar
  • 15 Manipalviratn S, DeCherney A, Segars J. Imprinting disorders and assisted reproductive technology. Fertil Steril 2009; 91 (02) 305-315
    CrossrefPubMedGoogle Scholar
  • 16 Clarke HJ, Vieux KF. Epigenetic inheritance through the female germ-line: the known, the unknown, and the possible. Semin Cell Dev Biol 2015; 43: 106-116
    CrossrefPubMedGoogle Scholar
  • 17 Eckersley-Maslin MA, Alda-Catalinas C, Reik W. Dynamics of the epigenetic landscape during the maternal-to-zygotic transition. Nat Rev Mol Cell Biol 2018; 19 (07) 436-450
    PubMedGoogle Scholar
  • 18 Howlett SK, Reik W. Methylation levels of maternal and paternal genomes during preimplantation development. Development 1991; 113 (01) 119-127
    PubMedGoogle Scholar
  • 19 Lucifero D, Chaillet JR, Trasler JM. Potential significance of genomic imprinting defects for reproduction and assisted reproductive technology. Hum Reprod Update 2004; 10 (01) 3-18
    CrossrefPubMedGoogle Scholar
  • 20 Kohda T. Effects of embryonic manipulation and epigenetics. J Hum Genet 2013; 58 (07) 416-420
    CrossrefPubMedGoogle Scholar
  • 21 El-Maarri O, Buiting K, Peery EG. , et al. Maternal methylation imprints on human chromosome 15 are established during or after fertilization. Nat Genet 2001; 27 (03) 341-344
    CrossrefPubMedGoogle Scholar
  • 22 Marchesi DE, Qiao J, Feng HL. Embryo manipulation and imprinting. Semin Reprod Med 2012; 30 (04) 323-334
    Article in Thieme ConnectPubMedGoogle Scholar
  • 23 Bourc'his D, Le Bourhis D, Patin D. , et al. Delayed and incomplete reprogramming of chromosome methylation patterns in bovine cloned embryos. Curr Biol 2001; 11 (19) 1542-1546
    CrossrefPubMedGoogle Scholar
  • 24 Doherty AS, Mann MR, Tremblay KD, Bartolomei MS, Schultz RM. Differential effects of culture on imprinted H19 expression in the preimplantation mouse embryo. Biol Reprod 2000; 62 (06) 1526-1535
    CrossrefPubMedGoogle Scholar
  • 25 Kawai K, Harada T, Ishikawa T. , et al. Parental age and gene expression profiles in individual human blastocysts. Sci Rep 2018; 8 (01) 2380
    CrossrefPubMedGoogle Scholar
  • 26 Khoueiry R, Ibala-Rhomdane S, Méry L. , et al. Dynamic CpG methylation of the KCNQ1OT1 gene during maturation of human oocytes. J Med Genet 2008; 45 (09) 583-588
    CrossrefPubMedGoogle Scholar
  • 27 Fauque P. Ovulation induction and epigenetic anomalies. Fertil Steril 2013; 99 (03) 616-623
    CrossrefPubMedGoogle Scholar
  • 28 Pfeifer S, Fritz M, Goldberg J. , et al; Practice Committees of the American Society for Reproductive Medicine and the Society for Assisted Reproductive Technology. In vitro maturation: a committee opinion. Fertil Steril 2013; 99 (03) 663-666
    CrossrefPubMedGoogle Scholar
  • 29 Anckaert E, De Rycke M, Smitz J. Culture of oocytes and risk of imprinting defects. Hum Reprod Update 2013; 19 (01) 52-66
    CrossrefPubMedGoogle Scholar
  • 30 DeChiara TM, Robertson EJ, Efstratiadis A. Parental imprinting of the mouse insulin-like growth factor II gene. Cell 1991; 64 (04) 849-859
    CrossrefPubMedGoogle Scholar
  • 31 Gabory A, Ripoche MA, Le Digarcher A. , et al. H19 acts as a trans regulator of the imprinted gene network controlling growth in mice. Development 2009; 136 (20) 3413-3421
    CrossrefPubMedGoogle Scholar
  • 32 Gicquel C, Rossignol S, Cabrol S. , et al. Epimutation of the telomeric imprinting center region on chromosome 11p15 in Silver-Russell syndrome. Nat Genet 2005; 37 (09) 1003-1007
    CrossrefPubMedGoogle Scholar
  • 33 Soejima H, Higashimoto K. Epigenetic and genetic alterations of the imprinting disorder Beckwith-Wiedemann syndrome and related disorders. J Hum Genet 2013; 58 (07) 402-409
    CrossrefPubMedGoogle Scholar
  • 34 Borghol N, Lornage J, Blachère T, Sophie Garret A, Lefèvre A. Epigenetic status of the H19 locus in human oocytes following in vitro maturation. Genomics 2006; 87 (03) 417-426
    CrossrefPubMedGoogle Scholar
  • 35 Kuhtz J, Romero S, De Vos M, Smitz J, Haaf T, Anckaert E. Human in vitro oocyte maturation is not associated with increased imprinting error rates at LIT1, SNRPN, PEG3 and GTL2. Hum Reprod 2014; 29 (09) 1995-2005
    CrossrefPubMedGoogle Scholar
  • 36 Virant-Klun I, Bauer C, Ståhlberg A, Kubista M, Skutella T. Human oocyte maturation in vitro is improved by co-culture with cumulus cells from mature oocytes. Reprod Biomed Online 2018; 36 (05) 508-523
    CrossrefPubMedGoogle Scholar
  • 37 Lu C, Zhang Y, Zheng X. , et al. Current perspectives on in vitro maturation and its effects on oocyte genetic and epigenetic profiles. Sci China Life Sci 2018; 61 (06) 633-643
    CrossrefPubMedGoogle Scholar
  • 38 Palermo GD, O'Neill CL, Chow S. , et al. Intracytoplasmic sperm injection: state of the art in humans. Reproduction 2017; 154 (06) F93-F110
    CrossrefPubMedGoogle Scholar
  • 39 Oliva R. Protamines and male infertility. Hum Reprod Update 2006; 12 (04) 417-435
    CrossrefPubMedGoogle Scholar
  • 40 Rajender S, Avery K, Agarwal A. Epigenetics, spermatogenesis and male infertility. Mutat Res 2011; 727 (03) 62-71
    PubMedGoogle Scholar
  • 41 Carrell DT. Epigenetics of the male gamete. Fertil Steril 2012; 97 (02) 267-274
    CrossrefPubMedGoogle Scholar
  • 42 Hammoud SS, Nix DA, Hammoud AO, Gibson M, Cairns BR, Carrell DT. Genome-wide analysis identifies changes in histone retention and epigenetic modifications at developmental and imprinted gene loci in the sperm of infertile men. Hum Reprod 2011; 26 (09) 2558-2569
    CrossrefPubMedGoogle Scholar
  • 43 Sutcliffe AG, Ludwig M. Outcome of assisted reproduction. Lancet 2007; 370 (9584): 351-359
    CrossrefPubMedGoogle Scholar
  • 44 Horsthemke B, Buiting K. Genomic imprinting and imprinting defects in humans. Adv Genet 2008; 61: 225-246
    PubMedGoogle Scholar
  • 45 Sharma R, Agarwal A, Rohra VK, Assidi M, Abu-Elmagd M, Turki RF. Effects of increased paternal age on sperm quality, reproductive outcome and associated epigenetic risks to offspring. Reprod Biol Endocrinol 2015; 13: 35
    CrossrefPubMedGoogle Scholar
  • 46 Houshdaran S, Cortessis VK, Siegmund K, Yang A, Laird PW, Sokol RZ. Widespread epigenetic abnormalities suggest a broad DNA methylation erasure defect in abnormal human sperm. PLoS One 2007; 2 (12) e1289
    CrossrefPubMedGoogle Scholar
  • 47 Kanber D, Buiting K, Zeschnigk M, Ludwig M, Horsthemke B. Low frequency of imprinting defects in ICSI children born small for gestational age. Eur J Hum Genet 2009; 17 (01) 22-29
    PubMedGoogle Scholar
  • 48 Palermo GD, Neri QV, Fields T, Rosenwaks Z. Popularity of ICSI. In: Schlegel PN. , ed. Biennial Review of Infertility. New York: Springer Sciences; 2013
    Google Scholar
  • 49 Estill MS, Bolnick JM, Waterland RA, Bolnick AD, Diamond MP, Krawetz SA. Assisted reproductive technology alters deoxyribonucleic acid methylation profiles in bloodspots of newborn infants. Fertil Steril 2016; 106 (03) 629-639 .e10
    CrossrefPubMedGoogle Scholar
  • 50 Dominguez-Salas P, Moore SE, Baker MS. , et al. Maternal nutrition at conception modulates DNA methylation of human metastable epialleles. Nat Commun 2014; 5: 3746
    CrossrefPubMedGoogle Scholar
  • 51 Levin I, Almog B, Shwartz T. , et al. Effects of laser polar-body biopsy on embryo quality. Fertil Steril 2012; 97 (05) 1085-1088
    CrossrefPubMedGoogle Scholar
  • 52 Carney SK, Das S, Blake D, Farquhar C, Seif MM, Nelson L. Assisted hatching on assisted conception (in vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI). Cochrane Database Syst Rev 2012; 12: CD001894
    PubMedGoogle Scholar
  • 53 Honguntikar SD, Salian SR, D'Souza F, Uppangala S, Kalthur G, Adiga SK. Epigenetic changes in preimplantation embryos subjected to laser manipulation. Lasers Med Sci 2017; 32 (09) 2081-2087
    CrossrefPubMedGoogle Scholar
  • 54 Shapiro BS, Daneshmand ST, Garner FC, Aguirre M, Hudson C. Clinical rationale for cryopreservation of entire embryo cohorts in lieu of fresh transfer. Fertil Steril 2014; 102 (01) 3-9
    CrossrefPubMedGoogle Scholar
  • 55 Yao J, Geng L, Huang R. , et al. Effect of vitrification on in vitro development and imprinted gene Grb10 in mouse embryos. Reproduction 2017; 154 (03) 97-105
    PubMedGoogle Scholar
  • 56 Wang S, Cowan CA, Chipperfield H, Powers RD. Gene expression in the preimplantation embryo: in-vitro developmental changes. Reprod Biomed Online 2005; 10 (05) 607-616
    CrossrefPubMedGoogle Scholar
  • 57 Cheng KR, Fu XW, Zhang RN, Jia GX, Hou YP, Zhu SE. Effect of oocyte vitrification on deoxyribonucleic acid methylation of H19, Peg3, and Snrpn differentially methylated regions in mouse blastocysts. Fertil Steril 2014; 102 (04) 1183-1190.e3
    CrossrefPubMedGoogle Scholar
  • 58 Derakhshan-Horeh M, Abolhassani F, Jafarpour F. , et al. Vitrification at Day 3 stage appears not to affect the methylation status of H19/IGF2 differentially methylated region of in vitro produced human blastocysts. Cryobiology 2016; 73 (02) 168-174
    CrossrefPubMedGoogle Scholar
  • 59 Melamed N, Choufani S, Wilkins-Haug LE, Koren G, Weksberg R. Comparison of genome-wide and gene-specific DNA methylation between ART and naturally conceived pregnancies. Epigenetics 2015; 10 (06) 474-483
    CrossrefPubMedGoogle Scholar
  • 60 Weksberg R, Smith AC, Squire J, Sadowski P. Beckwith-Wiedemann syndrome demonstrates a role for epigenetic control of normal development. Hum Mol Genet 2003; 12 (Spec No 1): R61-R68
    CrossrefPubMedGoogle Scholar
  • 61 Weksberg R, Shuman C, Beckwith JB. Beckwith-Wiedemann syndrome. Eur J Hum Genet 2010; 18 (01) 8-14
    CrossrefPubMedGoogle Scholar
  • 62 Lennerz JK, Timmerman RJ, Grange DK, DeBaun MR, Feinberg AP, Zehnbauer BA. Addition of H19 ‘loss of methylation testing’ for Beckwith-Wiedemann syndrome (BWS) increases the diagnostic yield. J Mol Diagn 2010; 12 (05) 576-588
    CrossrefPubMedGoogle Scholar
  • 63 Bliek J, Terhal P, van den Bogaard MJ. , et al. Hypomethylation of the H19 gene causes not only Silver-Russell syndrome (SRS) but also isolated asymmetry or an SRS-like phenotype. Am J Hum Genet 2006; 78 (04) 604-614
    CrossrefPubMedGoogle Scholar
  • 64 Chopra M, Amor DJ, Sutton L, Algar E, Mowat D. Russell-Silver syndrome due to paternal H19/IGF2 hypomethylation in a patient conceived using intracytoplasmic sperm injection. Reprod Biomed Online 2010; 20 (06) 843-847
    CrossrefPubMedGoogle Scholar
  • 65 Van Buggenhout G, Fryns J-P. Angelman syndrome (AS, MIM 105830). Eur J Hum Genet 2009; 17 (11) 1367-1373
    PubMedGoogle Scholar
  • 66 Moll AC, Imhof SM, Schouten-van Meeteren AY, van Leeuwen FE. In-vitro fertilisation and retinoblastoma. Lancet 2003; 361 (9366): 1392
    PubMedGoogle Scholar
  • 67 Barbosa RH, Vargas FR, Lucena E, Bonvicino CR, Seuánez HN. Constitutive RB1 mutation in a child conceived by in vitro fertilization: implications for genetic counseling. BMC Med Genet 2009; 10: 75
    PubMedGoogle Scholar
  • 68 Dommering CJ, van der Hout AH, Meijers-Heijboer H, Marees T, Moll AC. IVF and retinoblastoma revisited. Fertil Steril 2012; 97 (01) 79-81
    CrossrefPubMedGoogle Scholar
  • 69 White CR, Denomme MM, Tekpetey FR, Feyles V, Power SG, Mann MR. High frequency of imprinted methylation errors in human preimplantation embryos. Sci Rep 2015; 5: 17311
    CrossrefPubMedGoogle Scholar
  • 70 Ibala-Romdhane S, Al-Khtib M, Khoueiry R, Blachère T, Guérin JF, Lefèvre A. Analysis of H19 methylation in control and abnormal human embryos, sperm and oocytes. Eur J Hum Genet 2011; 19 (11) 1138-1143
    PubMedGoogle Scholar
  • 71 El Hajj N, Haertle L, Dittrich M. , et al. DNA methylation signatures in cord blood of ICSI children. Hum Reprod 2017; 32 (08) 1761-1769
    CrossrefPubMedGoogle Scholar
  • 72 Rabinowitz M, Ryan A, Gemelos G. , et al. Origins and rates of aneuploidy in human blastomeres. Fertil Steril 2012; 97 (02) 395-401
    CrossrefPubMedGoogle Scholar
  • 73 McCallie BR, Parks JC, Patton AL, Griffin DK, Schoolcraft WB, Katz-Jaffe MG. Hypomethylation and genetic instability in monosomy blastocysts may contribute to decreased implantation potential. PLoS One 2016; 11 (07) e0159507
    CrossrefPubMedGoogle Scholar
  • 74 Hammoud SS, Purwar J, Pflueger C, Cairns BR, Carrell DT. Alterations in sperm DNA methylation patterns at imprinted loci in two classes of infertility. Fertil Steril 2010; 94 (05) 1728-1733
    CrossrefPubMedGoogle Scholar
  • 75 Denomme MM, McCallie BR, Parks JC, Booher K, Schoolcraft WB, Katz-Jaffe MG. Inheritance of epigenetic dysregulation from male factor infertility has a direct impact on reproductive potential. Fertil Steril 2018; 110 (03) 419-428.e1
    CrossrefPubMedGoogle Scholar
  • 76 Urich MA, Nery JR, Lister R, Schmitz RJ, Ecker JR. MethylC-seq library preparation for base-resolution whole-genome bisulfite sequencing. Nat Protoc 2015; 10 (03) 475-483
    CrossrefPubMedGoogle Scholar
  • 77 Meissner A, Mikkelsen TS, Gu H. , et al. Genome-scale DNA methylation maps of pluripotent and differentiated cells. Nature 2008; 454 (7205): 766-770
    PubMedGoogle Scholar
  • 78 Smith ZD, Gu H, Bock C, Gnirke A, Meissner A. High-throughput bisulfite sequencing in mammalian genomes. Methods 2009; 48 (03) 226-232
    CrossrefPubMedGoogle Scholar
  • 79 Zhao MT, Whyte JJ, Hopkins GM, Kirk MD, Prather RS. Methylated DNA immunoprecipitation and high-throughput sequencing (MeDIP-seq) using low amounts of genomic DNA. Cell Reprogram 2014; 16 (03) 175-184
    CrossrefPubMedGoogle Scholar
  • 80 Bibikova M, Barnes B, Tsan C. , et al. High density DNA methylation array with single CpG site resolution. Genomics 2011; 98 (04) 288-295
    CrossrefPubMedGoogle Scholar
  • 81 Dedeurwaerder S, Defrance M, Calonne E, Denis H, Sotiriou C, Fuks F. Evaluation of the Infinium methylation 450K technology. Epigenomics 2011; 3 (06) 771-784
    CrossrefPubMedGoogle Scholar
  • 82 Fazzari MJ, Greally JM. Introduction to epigenomics and epigenome-wide analysis. Methods Mol Biol 2010; 620: 243-265
    PubMedGoogle Scholar
  • 83 Messerschmidt DM, Knowles BB, Solter D. DNA methylation dynamics during epigenetic reprogramming in the germline and preimplantation embryos. Genes Dev 2014; 28 (08) 812-828
    CrossrefPubMedGoogle Scholar