Abstract
Experimental embryology achievements in the century resulted in the birth of the first child conceived artificially. Besides its obvious social significance, the successful solution of the “test-tube babies” provided also the unique chance for direct inspection of human embryos growing in vitro at their earlier stages. New technologies applied for human gametes and earlier embryos studies, combined with high resolution capacities of modern cytogenetic and molecular methods, helped a lot in elaboration of efficient algorithms for assisted reproductive technologies (ART) and also provided a solid background for illumination of many genetic problems of human development before implantation. The later include input of chromosome aberrations and genome imprinting in pathology of early human development, cytogenetic and molecular mechanisms of the primary embryonic differentiation, genome epigenetic changes from fertilization through cleavage and blastulation, and identification of genes responsible for early development and differentiation. Conspicuous achievements in ART also include the creation of three parental embryos as a new step for the treatment of mitochondrial diseases, elaboration of karyomapping technique amenable for the diagnostics of both chromosomal and genetic pathology, and participation of paternal mitochondria delivered by the sperm in human development. A new era in human development genetics and ART was recently mitigated by the genome editing technique. The necessity of strict regulations for the safe implementation of genome editing in human embryonic development has been stressed. The areas of special attention include all studies of genome editing, production of artificial gametes, growing of chimera embryos for the purposes of organ and tissue transplantation, etc. Conspicuous delay of Russian science in the field of human developmental biology and experimental embryology and the necessity of its urgent support from both the fundamental sciences and clinical medicine have to be stressed.
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REFERENCES
Lukin, V.A., Leonov, B.V., Kalinina, E.A., et al., Successful completion of pregnancy after fertilization of eggs in vitro and transfer of embryos into the woman’s uterus, Akush. Ginekol. (Moscow), 1988, vol. 644, pp. 38–41.
Nikitin, A.I., Kitaev, E.M., Savitskii, G.A., et al., In vitro fertilization in humans, followed by successful embryo transplantation and the birth of a child, Arkh. Anat., Gistol. Embriol., 1987, vol. 9, no. 10, pp. 39–43.
Kushnir, V.A., Barad, D.H., Albertini, D.F., et al., Systematic review of worldwide trends in assisted re-productive technology 2004–2013, Reprod. Biol. Endocrinol., 2017, vol. 15, no. 1, p. 6. https://doi.org/10.1186/s12958-016-0225-2
Registr ART, Report 2016. http://rahr.ru/d_registr_otchet/RegistrART2016.pdf. Accessed April, 22, 2019.
Imudia, A.N. and Plosker, S., The past, present, and future of preimplantation genetic testing, Clin. Lab. Med., 2016, vol. 36, no. 2, pp. 385–399. https://doi.org/10.1016/j.cll.2016.01.012
SenGupta, S.B., Dhanjal, S., and Harper, J.C., Quality control standards in PGD and PGS, Reprod. Biomed. Online, 2016, vol. 32, no. 3, pp. 263–270. https://doi.org/10.1016/j.rbmo.2015.11.020
Sermon, K., Novel technologies emerging for preimplantation genetic diagnosis and preimplantation genetic testing for aneuploidy, Expert. Rev. Mol. Diagn., 2017, vol. 17, no. 1, pp. 71–82. https://doi.org/10.1080/14737159.2017.1262261
Handyside, A.H., Harton, G.L., Mariani, B., et al., Karyomapping: a universal method for genome wide analysis of genetic disease based on mapping crossovers between parental haplotypes, J. Med. Genet., 2010, vol. 47, no. 10, pp. 651–658. https://doi.org/10.1136/jmg.2009.069971
Griffin, D.K. and Ogur, C., Chromosomal analysis in IVF: just how useful is it?, Reproduction, 2018, vol. 156, no. 1, pp. F29–F50. https://doi.org/10.1530/REP-17-0683
Baranov, V.S. and Kuznetsova, T.V., Tsitogenetika embrional’nogo razvitiya cheloveka: nauchno-prakticheskie aspekty (Cytogenetics of Human Embryonic Development: Scientific and Practical Aspects), St. Petersburg: N-L, 2007.
Lebedev, I.N., Cytogenetics of human embryonic development: historical aspects and modern concepts, in Molekulyarno-biologicheskie tekhnologii v meditsinskoi praktike (Molecular Biological Technologies in Medical Practice), Novosibirsk: Al’fa-Vista N, 2008, issue 12, pp. 127—140.
Chiryaeva, O.G., Pendina, A.A., Tikhonov, A.V., et al., Comparative analysis of karyotype abnormalities in a pregnancy loss that happened naturally and with the use of assisted reproductive technologies, Zh. Akush. Zhen. Bolezn., 2012, vol. 61, no. 3, pp. 132–140. https://doi.org/10.1159/000446099
Pendina, A.A., Efimova, O. A., Chiryaeva, O.G., et al., A comparative cytogenetic study of miscarriages after IVF and natural conception in women aged under and over 35 years, J. Assist. Reprod. Genet., 2014, vol. 31, no. 2, pp. 149–155. https://doi.org/10.1007/s10815-013-0148-1
Wu, T., Yin, B., Zhu, Y., et al., Molecular cytogenetic analysis of early spontaneous abortions conceived from varying assisted reproductive technology procedures, Mol. Cytogenet., 2016, vol. 9, p. 79. https://doi.org/10.1186/s13039-016-0284-2
McCoy, R.C., Mosaicism in preimplantation human embryos: when chromosomal abnormalities are the norm, Trends Genet., 2017, vol. 33, no. 7, pp. 448–463. https://doi.org/10.1016/j.tig.2017.04.001
Su, Y., Li, J.J., Wang, C., et al., Aneuploidy analysis in day 7 human blastocysts produced by in vitro fertilization, Reprod. Biol. Endocrinol., 2016, vol. 14, no. 20, p. 1. https://doi.org/10.1186/s12958-016-0157-x
Munné, S., Blazek, J., Large, M., et al., Detailed investigation into the cytogenetic constitution and pregnancy outcome of replacing mosaic blastocysts detected with the use of high-resolution next-generation sequencing, Fertil. Steril., 2017, vol. 108, no. 1, pp. 62–71. https://doi.org/10.1016/j.fertnstert.2017.05.002
Lee, A. and Kiessling, A.A., Early human embryos are naturally aneuploid—can that be corrected?, J. Assist. Reprod. Genet., 2017, vol. 34, no. 1, pp. 15–21. https://doi.org/10.1007/s10815-016-0845-7
Dyban, A.P. and Baranov, V.S., Cytogenetics of Mammalian Embryonic Development, Oxford: Clarendon Press, 1987.
Taylor, T.H., Gitlin, S.A., Patrick, J.L., et al., The origin, mechanisms, incidence and clinical consequences of chromosomal mosaicism in humans, Hum. Reprod. Update, 2014, vol. 20, no. 4, pp. 571–581. https://doi.org/10.1093/humupd/dmu016
Vázquez-Diez, C. and FitzHarris, G. Causes and consequences of chromosome segregation error in preimplantation embryos, Reproduction, 2018, vol. 155, no. 1, pp. R63–R76. https://doi.org/10.1530/REP-17-0569
van de Werken, C., Avo, SantosM., Laven, J.S., et al., Chromosome segregation regulation in human zygotes: altered mitotic histone phosphorylation dynamics underlying centromeric targeting of the chromosomal passenger complex, Hum. Reprod., 2015, vol. 30, no. 10, pp. 2275–2291. https://doi.org/10.1093/humrep/dev186
Babariya, D., Fragouli, E., Alfarawati, S., et al., The incidence and origin of segmental aneuploidy in human oocytes and preimplantation embryos, Hum. Reprod., 2017, vol. 32, no. 12, pp. 2549–2560. https://doi.org/10.1093/humrep/dex324
Treff, N.R. and Franasiak, J.M., Detection of segmental aneuploidy and mosaicism in the human preimplantation embryo: technical considerations and limitations, Fertil. Steril., 2017, vol. 107, no. 1, pp. 27–31. https://doi.org/10.1016/j.fertnstert.2016.09.039
Sachdev, N.M., Maxwell, S.M., Besser, A.G., and Grifo, J.A., Diagnosis and clinical management of embryonic mosaicism, Fertil. Steril., 2017, vol. 107, no. 1, pp. 6–11. https://doi.org/10.1016/j.fertnstert.2016.10.006
Gleicher, N. and Orvieto, R., Is the hypothesis of preimplantation genetic screening (PGS) still supportable? A review, J. Ovarian Res., 2017, vol. 10, no. 1, p. 21. https://doi.org/10.1186/s13048-017-0318-3
Victor, A.R., Griffin, D.K., Brake, A.J., et al., Assessment of aneuploidy concordance between clinical trophectoderm biopsy and blastocyst, Hum. Reprod., 2019, vol. 34, no. 1, pp. 181–192. https://doi.org/10.1093/humrep/dey327
Esfandiari, N., Bunnell, M.E., and Casper, R.F., Human embryo mosaicism: did we drop the ball on chromosomal testing?, J. Assist. Reprod. Genet., 2016, vol. 33, no. 11, pp. 1439—1444.
Skryabin, N.A., Lebedev, I.N., Artyukhova, V.G., et al., Molecular karyotyping of cell-free DNA from blastocoele fluid as a basis for noninvasive preimplantation genetic screening of aneuploidy, Russ. J. Genet., 2015, vol. 51, no. 11, pp. 1123–1128. https://doi.org/10.1134/S1022795415110150
Tšuiko, O., Zhigalina, D.I., Jatsenko, T., et al., Karyotype of the blastocoel fluid demonstrates low concordance with both trophectoderm and inner cell mass, Fertil. Steril., 2018, vol. 109, no. 6, pp. 1127–1134. https://doi.org/10.1016/j.fertnstert.2018.02.008
Bolton, H., Graham, S.J.L., van der Aa, N., et al., Mouse model of chromosome mosaicism reveals lineage-specific depletion of aneuploid cells and normal developmental potential, Nat. Commun., 2016, vol. 7, p. 11165. https://doi.org/10.1038/ncomms11165
Kushnir, V.A., Darmon, S.K., Barad, D.H., and Gleicher, N., Degree of mosaicism in trophectoderm does not predict pregnancy potential: a corrected analysis of pregnancy outcomes following transfer of mosaic embryos, Reprod. Biol. Endocrinol., 2018, vol. 16, no. 1, p. 6. https://doi.org/10.1186/s12958-018-0322-5
Position Statement on Chromosome Mosaicism and Preimplantation Aneuploidy Testing at the Blastocyst Stage, Newsletter, July 19, 2016. http://www.pgdis.org/docs/newsletter_071816.html.
COGEN Position Statement on Chromosomal Mosaicism Detected in Preimplantation Blastocyst Biopsies. https://ivf-worldwide.com/cogen/general/cogen-statement.html.
Handyside, A.H., Live births following karyomapping—a “key” milestone in the development of preimplantation genetic diagnosis, Reprod. Biomed. Online, 2015, vol. 31, no. 3, pp. 307–308. https://doi.org/10.1016/j.rbmo.2015.07.003
Natesan, S.A., Handyside, A.H., Thornhill, A.R., et al., Live birth after PGD with confirmation by a comprehensive approach (karyomapping) for simultaneous detection of monogenic and chromosomal disorders, Reprod. Biomed. Online, 2014, vol. 29, no. 5, pp. 600–605. https://doi.org/10.1016/j.rbmo.2014.07.007
Ferguson-Smith, A. and Bourc’his, D., The discovery and importance of genomic imprinting, eLife, 2018, vol. 7. e 2368. https://doi.org/10.7554/eLife.42368
Sazhenova, E.A. and Lebedev, I.N., Cytogenetic and epigenetic aspects of hydatidiform moles, in Molekulyarno-biologicheskie tekhnologii v meditsinskoi praktike (Molecular Biological Technologies in Medical Practice), Novosibirsk: Al’fa-Vista, 2008, issue 12, pp. 151–161.
Lepshin, M.V., Sazhenova, E.A. and Lebedev, I.N., Multiple epimutations in imprinted genes in the human genome and congenital disorders, Russ. J. Genet., 2014, vol. 50, no. 3, pp. 221–236. https://doi.org/10.1134/S1022795414030053
Sazhenova, E.A., Nikitina, T.V., Skryabin, N.A., et al., Epigenetic status of imprinted genes in placenta during recurrent pregnancy loss, Russ. J. Genet., 2017, vol. 53, no. 3, pp. 376–387. https://doi.org/10.1134/S1022795417020090
Huntriss, J., Balen, A.H., Sinclair, K.D., et al., on behalf of the Royal College of Obstetricians and Gynaecologists, Epigenetics and Reproductive Medicine. Scientific Impact Paper no. 57, BJOG, 2018, vol. 125, no. 13: e43–e54. https://doi.org/10.1111/1471-0528.15240
Takahashi, N., Coluccio, A., Thorball, C.W., et al., ZNF445 is a primary regulator of genomic imprinting, Genes Dev., 2019, vol. 33, nos. 1–2, pp. 49–54. https://doi.org/10.1101/gad.320069.118
Sazhenova, E.A. and Lebedev, I.N., Molecular mechanisms of imprinted gene disorders in pathology of pre- and postnatal development, Med. Genet., 2018, vol. 17, no. 11, pp. 3–6. https://doi.org/10.25557/2073-7998.2018.11.3-6
Li, Z.K., Wang, L.Y., Wang, L.B., et al., Generation of uniparental mice from hypomethylated haploid ESCs with imprinting region deletions, Cell Stem Cell, 2018, vol. 23, no. 5, pp. 665–676. https://doi.org/10.1016/j.stem.2018.09.004
Jiang, Z., Wang, Y., Lin, J., et al., Genetic and epigenetic risks of assisted reproduction, Best Pract. Res. Clin. Obstet. Gynaecol., 2017, vol. 44, pp. 90–104. https://doi.org/10.1016/j.bpobgyn.2017.07.004
Hattori, H., Hiura, H., Kitamura, A., et al., Association of four imprinting disorders and ART, Clin. Epigenet., 2019, vol. 11, no. 1, p. 21. https://doi.org/10.1186/s13148-019-0623-3
Xu, J., Zhang, M., Niu, W., et al., Genome-wide uniparental disomy screen in human discarded morphologically abnormal embryos, Sci. Rep., 2015, vol. 5, p. 12302. https://doi.org/10.1038/srep12302
Sazhenova, E.A. and Lebedev, I.N., Genomic imprinting and assisted reproductive technologies, in Molekulyarno-biologicheskie tekhnologii v meditsinskoi praktike (Molecular Biological Technologies in Medical Practice), Novosibirsk: Novosibirsk: Akademizdat, 2018, issue 27, pp. 105—116.
Baranov, V.S. and Kuznetsova, T.V., Human developmental genetics, in Nasledstvennye bolezni: natsional’noe rukovodstvo (Inherited Diseases: National Guidelines), Bochkov, N.P., Ginter, E.K., and Puzyrev, V.P., Eds., Moscow: GEOTAR-Media, 2012, pp. 81–125.
Baranov, V.S., Kuznetsova, T.V., Pendina, A.A., et al., Epigenetic mechanisms of normal and pathological human development, in Epigenetika (Epigenetics), Novosibirsk: Sib. Otd. Ross. Akad. Nauk, 2012, pp. 225–266.
On Human Gene Editing: International Summit Statement. https://www8.nationalacademies.org/onpinews/newsitem.aspx?RecordID=12032015a.
Munch, E.M., Sparks, A.E., and Gonzalez Bosquet, J., Differentially expressed genes in preimplantation human embryos: potential candidate genes for blastocyst formation and implantation, J. Assist. Reprod. Genet., 2016, vol. 33, no. 8, pp. 1017–1025. https://doi.org/10.1007/s10815-016-0745-x
Godini, R. and Fallahi, H., Dynamics changes in the transcription factors during early human embryonic development, J. Cell Physiol., 2019, vol. 234, no. 5, pp. 6489–6502. https://doi.org/10.1002/jcp.27386
Fogarty, N.M.E., McCarthy, A., Snijders, K.E., et al., Genome editing reveals a role for OCT4 in human embryogenesis, Nature, 2017, vol. 550, no. 7674, pp. 67–73. https://doi.org/10.1038/nature24033
Okada, Y. and Yamaguchi, K., Epigenetic modifications and reprogramming in paternal pronucleus: sperm, preimplantation embryo, and beyond, Cell Mol. Life Sci., 2017, vol. 74, no. 11, pp. 1957–1967. https://doi.org/10.1007/s00018-016-2447-z
Ke, Y., Xu, Y., Chen, X., et al., 3D chromatin structures of mature gametes and structural reprogramming during mammalian embryogenesis, Cell. 2017, vol. 170, no. 2, pp. 367–381. https://doi.org/10.1016/j.cell.2017.06.029
Eckersley-Maslin, M.A., Alda-Catalinas, C., and Reik, W., Dynamics of the epigenetic landscape during the maternal-to-zygotic transition, Nat. Rev. Mol. Cell Biol., 2018, vol. 19, no. 7, pp. 436–450. https://doi.org/10.1038/s41580-018-0008-z
Racko, D., Benedetti, F., Dorier, J., and Stasiak, A., Are TADs supercoiled?, Nucleic Acids Res., 2019, vol. 47, no. 2, pp. 521–532. https://doi.org/10.1093/nar/gky1091
Hug, C.B. and Vaquerizas, J.M., The birth of the 3D genome during early embryonic development, Trends Genet., 2018, vol. 34, no. 12, pp. 903–914. https://doi.org/10.1016/j.tig.2018.09.002
Lebedev, I.N., Human cytogenetics in genome and postgenome era: from genome architecture to novel chromosomal diseases, Tsitologiya, 2018, vol. 60, no. 7, pp. 499–502. https://doi.org/10.31116/tsitol.2018.07.02
Yamamoto, R. and Aoki, F., A unique mechanism regulating gene expression in 1 cell embryos, J. Reprod. Dev., 2017, vol. 63, no. 1, pp. 9–11. https://doi.org/10.1262/jrd.2016-133
Du, H., Zheng, B., Huang, R., et al., Allelic reprogramming of 3D chromatin architecture during early mammalian development, Nature, 2017, vol. 547, no. 7662, pp. 232–235. https://doi.org/10.1038/nature23263
Deglincerti, A., Croft, G.F., Pietila, L.N., et al., Self-organization of the in vitro attached human embryo, Nature, 2016, vol. 533, no. 7602, pp. 251–254. https://doi.org/10.1038/nature17948
Liu, G., Wang, W., Hu, S., et al., Inherited DNA methylation primes the establishment of accessible chromatin during genome activation, Genome Res., 2018, vol. 28, no. 7, pp. 998–1007. https://doi.org/10.1101/gr.228833.117
Wu, J., Xu, J., Liu, B., et al., Chromatin analysis in human early development reveals epigenetic transition during ZGA, Nature, 2018, vol. 557, no. 7704, pp. 256–260. https://doi.org/10.1038/s41586-018-0080-8
Fraser, R. and Lin, C.J., Epigenetic reprogramming of the zygote in mice and men: on your marks, get set, go! Reproduction, 2016, vol. 152, no. 6, pp. R211–R222. https://doi.org/10.1530/REP-16-0376
Petrussa, L., Van de Velde, H., and De Rycke, M., Similar kinetics for 5-methylcytosine and 5-hydroxymethylcytosine during human preimplantation development in vitro, Mol. Reprod. Dev., 2016, vol. 83, no. 7, pp. 594–605. https://doi.org/10.1002/mrd.22656
Baranov, V.S., Pendina, A.A., Kuznetsova, T.V., et al., Peculiarities of metaphase chromosome methylation pattern in preimplantation human embryos, Tsitologiya, 2005, vol. 47, no. 8, pp. 723–730.
Pendina, A.A., Efimova, O.A., Fedorova, I.D., et al., DNA methylation patterns of metaphase chromosomes in human preimplantation embryos, Cytogenet. Genome Res., 2011, vol. 132, nos. 1–2, pp. 1–7. https://doi.org/10.1159/000318673
Efimova, O.A., Pendina, A.A., Tikhonov, A.V., et al., Chromosome hydroxymethylation patterns in human zygotes and cleavage-stage embryos, Reproduction, 2015, vol. 149, no. 3, pp. 223–233. https://doi.org/10.1530/REP-14-0343
White, M.D., Angiolini, J.F., Alvarez, Y.D., et al., Long-lived binding of Sox2 to DNA predicts cell fate in the four-cell mouse embryo, Cell, 2016, vol. 165, no. 1, pp. 75–87. https://doi.org/10.1016/j.cell.2016.02.032
De Iaco, A., Planet, E., Coluccio, A., et al., DUX-family transcription factors regulate zygotic genome activation in placental mammals, Nat. Genet., vol. 49, no. 6, pp. 941–945. https://doi.org/10.1038/ng.3858
Geng, L.N., Yao, Z., Snider, L., et al., DUX4 activates germline genes, retroelements, and immune mediators: implications for facioscapulohumeral dystrophy, Dev. Cell., 2012, vol. 22, no. 1, pp. 38–51. https://doi.org/10.1016/j.devcel.2011.11.013
Morris, S.A., Human embryos cultured in vitro to 14 days, Open Biol., 2017, vol. 7, no. 1, p. 170003. https://doi.org/10.1098/rsob.170003
Knorre, A.G., Kratkii ocherk po embriologii cheloveka (A Brief Survey of Human Embryology), Leningrad: Meditsina, 1967.
Rossant, J., Human embryology: implantation barrier overcome, Nature, 2016, vol. 533, no. 7602, pp. 182–183. https://doi.org/10.1038/nature17894
Amato, P., Tachibana, M., Sparman, M., and Mitalipov, S., Three-parent in vitro fertilization: gene replacement for the prevention of inherited mitochondrial diseases, Fertil. Steril., 2014, vol. 101, no. 1, pp. 31–35. https://doi.org/10.1016/j.fertnstert.2013.11.030
Luo, S., Valencia, C.A., Zhang, J., et al., Biparental inheritance of mitochondrial DNA in humans, Proc. Natl. Acad. Sci. U.S.A., 2018, vol. 115, no. 51, pp. 13039–13044. https://doi.org/10.1073/pnas.1810946115
Yang, Y., Zhang, X., Yi, L., and Hou, Z., Naive induced pluripotent stem cells generated from β-thalassemia fibroblasts allow efficient gene correction with CRISP/Cas 9, Stem Cells Transl. Med., 2016, vol. 5, no. 1, pp. 8–19. https://doi.org/10.5966/sctm.2015-0157
Lanphier, E., Urnov, F., Heacker, S.E., et al., Do not edit human germ line, Nature, 2015, vol. 519, no. 7544, pp. 410–411. https://doi.org/10.1038/519410a
Ma, H., Marti-Gutierrez, N., Park, S.W., et al., Correction of a pathogenic gene mutation in human embryos, Nature, 2017, vol. 548, no. 7668, pp. 413–419. https://doi.org/10.1038/nature23305
Lander, E., Baylis, Fr., Zhang, F., et al., Adopt a moratorium on heritable genome editing, Nature, 2019, vol. 567, no. 7747, pp. 165–168. https://doi.org/10.1038/d41586-019-00726-5
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Baranov, V.S., Kogan, I.Y. & Kuznetzova, T.V. Advances in Developmental Genetics and Achievements in Assisted Reproductive Technology. Russ J Genet 55, 1171–1182 (2019). https://doi.org/10.1134/S1022795419100028
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DOI: https://doi.org/10.1134/S1022795419100028