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)

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.

 
  • 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
  • 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
  • 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
  • 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
  • 5 Owen CM, Segars Jr JH. Imprinting disorders and assisted reproductive technology. Semin Reprod Med 2009; 27 (05) 417-428
  • 6 Gosden R, Trasler J, Lucifero D, Faddy M. Rare congenital disorders, imprinted genes, and assisted reproductive technology. Lancet 2003; 361 (9373): 1975-1977
  • 7 Wolffe AP, Matzke MA. Epigenetics: regulation through repression. Science 1999; 286 (5439): 481-486
  • 8 Laprise SL. Implications of epigenetics and genomic imprinting in assisted reproductive technologies. Mol Reprod Dev 2009; 76 (11) 1006-1018
  • 9 Sasaki H, Matsui Y. Epigenetic events in mammalian germ-cell development: reprogramming and beyond. Nat Rev Genet 2008; 9 (02) 129-140
  • 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
  • 11 Lawrence LT, Moley KH. Epigenetics and assisted reproductive technologies: human imprinting syndromes. Semin Reprod Med 2008; 26 (02) 143-152
  • 12 Allegrucci C, Thurston A, Lucas E, Young L. Epigenetics and the germline. Reproduction 2005; 129 (02) 137-149
  • 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
  • 14 Reik W, Kelsey G. Epigenetics: cellular memory erased in human embryos. Nature 2014; 511 (7511): 540-541
  • 15 Manipalviratn S, DeCherney A, Segars J. Imprinting disorders and assisted reproductive technology. Fertil Steril 2009; 91 (02) 305-315
  • 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
  • 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
  • 18 Howlett SK, Reik W. Methylation levels of maternal and paternal genomes during preimplantation development. Development 1991; 113 (01) 119-127
  • 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
  • 20 Kohda T. Effects of embryonic manipulation and epigenetics. J Hum Genet 2013; 58 (07) 416-420
  • 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
  • 22 Marchesi DE, Qiao J, Feng HL. Embryo manipulation and imprinting. Semin Reprod Med 2012; 30 (04) 323-334
  • 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
  • 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
  • 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
  • 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
  • 27 Fauque P. Ovulation induction and epigenetic anomalies. Fertil Steril 2013; 99 (03) 616-623
  • 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
  • 29 Anckaert E, De Rycke M, Smitz J. Culture of oocytes and risk of imprinting defects. Hum Reprod Update 2013; 19 (01) 52-66
  • 30 DeChiara TM, Robertson EJ, Efstratiadis A. Parental imprinting of the mouse insulin-like growth factor II gene. Cell 1991; 64 (04) 849-859
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 39 Oliva R. Protamines and male infertility. Hum Reprod Update 2006; 12 (04) 417-435
  • 40 Rajender S, Avery K, Agarwal A. Epigenetics, spermatogenesis and male infertility. Mutat Res 2011; 727 (03) 62-71
  • 41 Carrell DT. Epigenetics of the male gamete. Fertil Steril 2012; 97 (02) 267-274
  • 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
  • 43 Sutcliffe AG, Ludwig M. Outcome of assisted reproduction. Lancet 2007; 370 (9584): 351-359
  • 44 Horsthemke B, Buiting K. Genomic imprinting and imprinting defects in humans. Adv Genet 2008; 61: 225-246
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 61 Weksberg R, Shuman C, Beckwith JB. Beckwith-Wiedemann syndrome. Eur J Hum Genet 2010; 18 (01) 8-14
  • 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
  • 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
  • 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
  • 65 Van Buggenhout G, Fryns J-P. Angelman syndrome (AS, MIM 105830). Eur J Hum Genet 2009; 17 (11) 1367-1373
  • 66 Moll AC, Imhof SM, Schouten-van Meeteren AY, van Leeuwen FE. In-vitro fertilisation and retinoblastoma. Lancet 2003; 361 (9366): 1392
  • 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
  • 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
  • 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
  • 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
  • 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
  • 72 Rabinowitz M, Ryan A, Gemelos G. , et al. Origins and rates of aneuploidy in human blastomeres. Fertil Steril 2012; 97 (02) 395-401
  • 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
  • 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
  • 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
  • 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
  • 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
  • 78 Smith ZD, Gu H, Bock C, Gnirke A, Meissner A. High-throughput bisulfite sequencing in mammalian genomes. Methods 2009; 48 (03) 226-232
  • 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
  • 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
  • 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
  • 82 Fazzari MJ, Greally JM. Introduction to epigenomics and epigenome-wide analysis. Methods Mol Biol 2010; 620: 243-265
  • 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