Skip to main content
Log in

In Vitro Modeling of the Early Development of Mouse and Human Embryos

  • REVIEWS
  • Published:
Russian Journal of Developmental Biology Aims and scope Submit manuscript

Abstract

Mammalian embryonic development includes preimplantation, implantation and post-implantation development, during which the embryo is attached to the uterus wall. The modeling of embryo development in culture allows to study the process of ontogenesis in its dynamic development, which is especially valuable for studying early post-implantation development. We reviewed existing cultivation systems for mouse and human embryos. Also we considered a new experimental approach for studying early mammalian embryogenesis—embryo-like cell constructs. Using these methods, the most important results were obtained about the formation of embryonic germ layers, which provided insights into the molecular and cellular mechanisms of morphogenesis of the mouse and human embryos. The purpose of this review is to generalize the possibilities and limitations of such systems for studying mammalian embryogenesis and to find directions for further development of this approach.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

REFERENCES

  1. Aach, J., Lunshof, J., Iyer, E., et al., Addressing the ethical issues raised by synthetic human entities with embryo-like features, Elife, 2017, vol. 6, pp. 1–20.

    Google Scholar 

  2. Ambrosi, D., Beloussov, L.V., and Ciarletta, P., Mechanobiology and morphogenesis in living matter: a survey, Meccanica, 2017, vol. 52, no. 14, pp. 3371–3387.

    Article  Google Scholar 

  3. Ashary, N., Tiwari, A., and Modi, D., Embryo implantation: war in times of love, Endocrinology, 2018, vol. 159, no. 2, pp. 1188–1198.

    Article  CAS  PubMed  Google Scholar 

  4. Beccari, L., Moris, N., Girgin, M., et al., Multi-axial self-organization properties of mouse embryonic stem cells into gastruloids, Nature, 2018, vol. 562, no. 7726, pp. 272–276.

    Article  CAS  PubMed  Google Scholar 

  5. Bedzhov, I. and Zernicka-Goetz, M., Self-organizing properties of mouse pluripotent cells initiate morphogenesis upon implantation, Cell, 2014, vol. 156, no. 5, pp. 1032–1044.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Bedzhov, I., Leung, C.Y., Bialecka, M., et al., In vitro culture of mouse blastocysts beyond the implantation stages, Nat. Protoc., 2014, vol. 9, no. 12, pp. 2732–2739.

    Article  CAS  PubMed  Google Scholar 

  7. Bedzhov, I., Bialecka, M., Zielinska, A., et al., Development of the anterior-posterior axis is a self-organizing process in the absence of maternal cues in the mouse embryo, Cell Res., 2015, vol. 25, no. 12, pp. 1368–1371.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Beloussov, L.V., Morphomechanics of Development, Springer International Publishing, 2015.

    Book  Google Scholar 

  9. Beloussov, L.V., Louchinskaia, N.N., and Stein, A.A., Tension-dependent collective cell movements in the early gastrula ectoderm of Xenopus laevis embryos, Dev. Genes Evol., 2000, vol. 210, no. 2, pp. 92–104.

    Article  CAS  PubMed  Google Scholar 

  10. Bentin-Ley, U., Horn, T., Sjogren, A., et al., Ultrastructure of human blastocyst-endometrial interactions in vitro, J. Reprod. Fertil., 2000, vol. 120, no. 2, pp. 337–350.

    Article  CAS  PubMed  Google Scholar 

  11. Berkhout, R.P., Lambalk, C.B., Huirne, J., et al., High-quality human preimplantation embryos actively influence endometrial stromal cell migration, J. Assist. Reprod. Genet., 2018, vol. 35, no. 4, pp. 659–667.

    Article  CAS  PubMed  Google Scholar 

  12. Bouillon, C., Leandri, R., Desch, L., et al., Does embryo culture medium influence the health and development of children born after in vitro fertilization?, PLoS One, 2016, vol. 11, no. 3, pp. 1–14.

    Article  CAS  Google Scholar 

  13. Brink, S.C., Alemany, A., Batenburg, V., et al., Symmetry breaking, germ layer specification and axial organisation in aggregates of mouse embryonic stem cells, Development, 2014, vol. 141, no. 22, pp. 4231–4242.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  14. Brosens, J.J., Salker, M.S., Teklenburg, G., et al., Uterine selection of human embryos at implantation, Sci. Rep., 2014, vol. 4, pp. 4–11.

    Google Scholar 

  15. Buck, V.U., Gellersen, B., Leube, R.E., et al., Interaction of human trophoblast cells with gland-like endometrial spheroids: a model system for trophoblast invasion, Hum. Reprod., 2015, vol. 30, no. 4, pp. 906–916.

    Article  CAS  PubMed  Google Scholar 

  16. Carson, D.D., Tang, J.P., and Gay, S., Collagens support embryo attachment and outgrowth in vitro: effects of the Arg-Gly-Asp sequence, Dev. Biol., 1988, vol. 127, no. 2, pp. 368–375.

    Article  CAS  PubMed  Google Scholar 

  17. Christodoulou, N., Weberling, A., Strathdee, D., et al., Morphogenesis of extra-embryonic tissues directs the remodelling of the mouse embryo at implantation, Nat. Commun., 2019, vol. 10, no. 1, pp. 1–12.

    Article  CAS  Google Scholar 

  18. Coucouvanis, E. and Martin, G.R., Signals for death and survival: a two-step mechanism for cavitation in the vertebrate embryo, Cell, 1995, vol. 83, no. 2, pp. 279–287.

    Article  CAS  PubMed  Google Scholar 

  19. Cuman, C., Menkhorst, E.M., Rombauts, L.J., et al., Preimplantation human blastocysts release factors that differentially alter human endometrial epithelial cell adhesion and gene expression relative to IVF success, Hum. Reprod., 2013, vol. 28, no. 5, pp. 1161–1171.

    Article  CAS  PubMed  Google Scholar 

  20. Deglincerti, A., Croft, G.F., Pietila, L.N., et al., Self-organization of the in vitro attached human embryo, Nature, 2016, vol. 533, pp. 251–254.

    Article  CAS  PubMed  Google Scholar 

  21. Doherty, A.S., Mann, M.R.W., Tremblay, K.D., et al., Differential effects of culture on imprinted H19 expression in the preimplantation mouse embryo1, Biol. Reprod., 2000, vol. 62, no. 6, pp. 1526–1535.

    Article  CAS  PubMed  Google Scholar 

  22. Domínguez, F., Simon, C., Quinonero, A., et al., Human endometrial CD98 is essential for blastocyst adhesion, PLoS One, 2010, vol. 5, no. 10.

  23. Drakou, K. and Georgiades, P., A serum-free and defined medium for the culture of mammalian postimplantation embryos, Biochem. Biophys. Res. Commun., 2015, vol. 468, no. 4, pp. 813–819.

    Article  CAS  PubMed  Google Scholar 

  24. Ecker, D.J., Stein, P., Xu, Z., et al., Long-term effects of culture of preimplantation mouse embryos on behavior, Proc. Natl. Acad. Sci. U. S. A., 2004, vol. 101, no. 6, pp. 1595–1600.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Edwards, R.G., Steptoe, P.C., and Purdy, J.M., Fertilization and cleavage in vitro of preovulatory human oocytes, 1971, pp. 287–289.

  26. Esteves, T.C., Rossem, F.V., Nordhoff, V., et al., A microfluidic system supports single mouse embryo culture leading to full-term development, RSC Adv., 2013, vol. 3, no. 48, pp. 26451–26458.

    Article  CAS  Google Scholar 

  27. Evans, J., Walker, K.J., Bilandzic, M., et al., A novel “embryo-endometrial” adhesion model can potentially predict “receptive or non-receptive” endometrium, J. Assist. Reprod. Genet., 2019.

  28. Fauque, P., Mondon, F., Letourneur, F., et al., In vitro fertilization and embryo culture strongly impact the placental transcriptome in the mouse model, PLoS One, 2010, vol. 5, no. 2.

  29. Gac, S. and Le Nordhoff, V., Microfluidics for mammalian embryo culture and selection: where do we stand now?, Mol. Hum. Reprod., 2017, vol. 23, no. 4, pp. 213–226.

    PubMed  Google Scholar 

  30. Gardner, D.K., Ex vivo early embryo development and effects on gene expression and imprinting, Reprod. Fertil. Dev., 2005, pp. 361–370.

  31. Giritharan, G., Piane, L., Donjacour, A., et al., In vitro culture of mouse embryos reduces differential gene expression between inner cell mass and trophectoderm, Reprod. Sci., 2012, vol. 19, no. 3, pp. 243–252.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Glanville-Jones, H.C., Woo, N., and Arkell, R.M., Successful whole embryo culture with commercially available reagents, Int. J. Dev. Biol., 2013, vol. 57, no. 1, pp. 61–67.

    Article  CAS  PubMed  Google Scholar 

  33. Harrison, S.E., Sozen, B., and Zernicka-Goetz, M., In vitro generation of mouse polarized embryo-like structures from embryonic and trophoblast stem cells, Nat. Protoc., 2018, vol. 13, no. 7, pp. 1586–1602.

    Article  CAS  PubMed  Google Scholar 

  34. Heo, Y.S., Cabrera, L., Bormann, C., et al., Dynamic microfunnel culture enhances mouse embryo development and pregnancy rates, Hum. Reprod., 2010, vol. 25, no. 3, pp. 613–622.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Hiramatsu, R., Matsuoka, T., Kimura-Yoshida, C., et al., External mechanical cues trigger the establishment of the anterior-posterior axis in early mouse embryos, Dev. Cell, 2013, vol. 27, no. 2, pp. 131–144.

    Article  CAS  PubMed  Google Scholar 

  36. Hsu, Y.C., Differentiation in vitro of mouse embryos to the stage of early somite, Dev. Biol., 1973, vol. 33, no. 2, pp. 403–411.

    Article  CAS  PubMed  Google Scholar 

  37. Hsu, Y.C., In vitro development of individually cultured whole mouse embryos from blastocyst to early somite stage, Dev. Biol., 1979, vol. 68, no. 2, pp. 453–461.

    Article  CAS  PubMed  Google Scholar 

  38. Hsu, Y.C. Baskar, J., et al., Development in vitro of mouse embryos from the two-cell egg stage to the early somite stage, Development, 1974, vol. 31, no. 1, pp. 235–245.

    CAS  Google Scholar 

  39. ISSCR, Guidelines for the Conduct of Human Embryonic Stem Cell Research, 2006.

  40. ISSCR, Guidelines for Stem Cell Research and Clinical Translation, 2016.

  41. Jenkinson, E.J. and Wilson, I.B., In vitro support system for the study of blastocyst differentiation in the mouse, Nature, 1970, vol. 228, pp. 227–231.

    Article  Google Scholar 

  42. Kalaskar, V.K. and Lauderdale, J.D., Mouse embryonic development in a serum-free whole embryo culture system, J. Vis. Exp., 2014, no. 85, pp. 1–8.

  43. Kaneko, Y., Day, M.L., and Murphy, C.R., Integrin β3 in rat blastocysts and epithelial cells is essential for implantation in vitro: studies with Ishikawa cells and small interfering RNA transfection, Hum. Reprod., 2011a, vol. 26, no. 7, pp. 1665–1674.

    Article  CAS  PubMed  Google Scholar 

  44. Kaneko, Y., Lecce, L., Day, M.L., et al., B1 and B3 integrins disassemble from basal focal adhesions and β3 integrin is later localised to the apical plasma membrane of rat uterine luminal epithelial cells at the time of implantation, Reprod. Fertil. Dev., 2011b, vol. 23, no. 3, pp. 481–495.

    Article  CAS  PubMed  Google Scholar 

  45. Kaneko, Y., Murphy, C.R., and Day, M.L., Extracellular matrix proteins secreted from both the endometrium and the embryo are required for attachment: a study using a co-culture model of rat blastocysts and Ishikawa cells, J. Morphol., 2013, vol. 274, no. 1, pp. 63–72.

    Article  CAS  PubMed  Google Scholar 

  46. Kang, Y.J., Forbes, K., Karver, J., et al., The role of the osteopontin–integrin αvβ3 interaction at implantation: functional analysis using three different in vitro models, Hum. Reprod., 2014, vol. 29, no. 4, pp. 739–749.

    Article  CAS  PubMed  Google Scholar 

  47. Kang, Y.J., Lees, M., Matthews, L.C., et al., miR-145 suppresses embryo-epithelial juxtacrine communication at implantation by modulating maternal IGF1R, J. Cell Sci., 2015, vol. 128, no. 4, pp. 804–814.

    Article  CAS  PubMed  Google Scholar 

  48. Kauma, S.W. and Matt, D.W., Coculture cells that express leukemia inhibitory factor (LIF) enhance mouse blastocyst development in vitro, J. Assist. Reprod. Genet., 1995, vol. 12, no. 2, pp. 153–156.

    Article  CAS  PubMed  Google Scholar 

  49. Khalifa, E.A.M., Tucker, M.J., and Hunt, P., Cruciate thinning of the zona pellucida for more successful enhancement of blastocyst hatching in the mouse, Hum. Reprod., 1992, vol. 7, no. 4, pp. 532–536.

    Article  CAS  PubMed  Google Scholar 

  50. Khosla, S., Dean, W., Brown, D., et al., Culture of preimplantation mouse embryos affects fetal development and the expression of imprinted genes1, Biol. Reprod., 2001, vol. 64, no. 3, pp. 918–926.

    Article  CAS  PubMed  Google Scholar 

  51. Kime, C., Kiyonari, H., Ohtsuka, S., et al., Induced 2C expression and implantation-competent blastocyst-like cysts from primed pluripotent stem cells, Stem Cell Rep., 2019, vol. 13, no. 3, pp. 485–498.

    Article  CAS  Google Scholar 

  52. Kleijkers, S.H.M., Montfurt, A.P.A., Bekers, O., et al., Ammonium accumulation in commercially available embryo culture media and protein supplements during storage at 2–8°C and during incubation at 37°C, Hum. Reprod., 2016, vol. 31, no. 6, pp. 1192–1199.

    Article  CAS  PubMed  Google Scholar 

  53. Kolahi, K.S., Donjacour, A., Xiaowei, L., et al., Effect of substrate stiffness on early mouse embryo development, PLoS One, 2012, vol. 7, no. 7.

  54. Li, R., Zhong, C., Yang, Y., et al., Generation of blastocyst-like structures from mouse embryonic and adult cell cultures, Cell, 2019, vol. 179, no. 3, pp. 687–702. е18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Ma, W., Song, H., Das, S.K., et al., Estrogen is a critical determinant that specifies the duration of the window of uterine receptivity for implantation, Proc. Natl. Acad. Sci. U. S. A., 2003, vol. 100, no. 5, pp. 2963–2968.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Mahdavinezhad, F., Kazemi, P., Fathalizadeh, P., et al., In vitro versus in vivo: development-, apoptosis-, and implantation-related gene expression in mouse blastocyst, Iran. J. Biotechnol., 2019, vol. 17, no. 1, pp. 90–97.

    Article  Google Scholar 

  57. Mantikou, E., Jonker, M.J., Wong, K.M., et al., Factors affecting the gene expression of in vitro cultured human preimplantation embryos, Hum. Reprod., 2016, vol. 31, no. 2, pp. 298–311.

    CAS  PubMed  Google Scholar 

  58. Morbeck, D.E., Krisher, R.L., Herrick, J.R., et al., Composition of commercial media used for human embryo culture, Fertil. Steril., 2014, vol. 102, no. 3.

  59. Morris, S.A., Grewal, S., Barrios, F., et al., Dynamics of anterior-posterior axis formation in the developing mouse embryo, Nat. Commun., 2012, vol. 3, pp. 610–673.

    Article  CAS  Google Scholar 

  60. Munsie, M., Hyun, I., and Sugarman, J., Ethical issues in human organoid and gastruloid research, Development, 2017, vol. 144, no. 6, pp. 942–945.

    Article  CAS  PubMed  Google Scholar 

  61. New, D.A., Development of rat embryos cultured in blood sera, J. Reprod. Fertil., 1966, vol. 12, no. 3, pp. 509–524.

    Article  CAS  PubMed  Google Scholar 

  62. Olalekan, S.A., Burdette, J.E., Getsios, S., et al., Development of a novel human recellularized endometrium that responds to a 28-day hormone treatment, Biol. Reprod., 2017, vol. 96, no. 5, pp. 971–981.

    Article  PubMed  PubMed Central  Google Scholar 

  63. Pera, M.F., DeWert, G., Dondorp, W., et al., What if stem cells turn into embryos in a dish?, Nat. Methods, 2015, vol. 12, no. 10, pp. 917–919.

    Article  CAS  PubMed  Google Scholar 

  64. Piliszek, A., Kwon, G.S., and Hadjantonakis, A.-K., Ex utero culture and live imaging of mouse embryos, Methods Mol. Biol., 2011, vol. 770, pp. 439–455.

    Article  CAS  Google Scholar 

  65. Rinaudo, P. and Schultz, R.M., Effects of embryo culture on global pattern of gene expression in preimplantation mouse embryos, Reproduction, 2004, vol. 128, no. 3, pp. 301–311.

    Article  CAS  PubMed  Google Scholar 

  66. Rivron, N.C., Frias-Aldeguer, J., Vrij, E.J., et al., Blastocyst-like structures generated solely from stem cells, Nature, 2018, vol. 557, no. 7703, pp. 106–111.

    Article  CAS  PubMed  Google Scholar 

  67. Roode, M., Blair, K., Snell, P., et al., Human hypoblast formation is not dependent on FGF signalling, Dev. Biol., 2012, vol. 361, no. 2, pp. 358–363.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Shahbazi, M.N., Jedrusik, A., Vuoristo, S., et al., Self-organisation of the human embryo in the absence of maternal tissues, Nat. Cell Biol., 2016, vol. 18, no. 6, pp. 700–708.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Shahbazi, M.N., Siggia, E.D., and Zernicka-Goetz, M., Self-organization of stem cells into embryos: a window on early mammalian development, Science, 2019, vol. 364, no. 6444, pp. 948–951.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Shao, Y., Taniguchi, K., Gurdziel, K., et al., Self-organized amniogenesis by human pluripotent stem cells in a biomimetic implantation-like niche, Nat. Mater., 2017a, vol. 16, no. 4, pp. 419–425.

    Article  CAS  PubMed  Google Scholar 

  71. Shao, Y., Taniguchi, K., Townshend, R.F., et al., A pluripotent stem cell-based model for post-implantation human amniotic sac development, Nat. Commun., 2017b, vol. 8, no. 1, pp. 1–15.

    Article  CAS  Google Scholar 

  72. Simón, C., Mercader, A., Garcia-Velasco, J., et al., Coculture of human embryos with autologous human endometrial epithelial cells in patients with implantation failure, J. Clin. Endocrinol. Metab., 1999, vol. 84, no. 8, pp. 2638–2646.

    PubMed  Google Scholar 

  73. Simunovic, M., Metzger, J.J., Etoc, F., et al., Molecular mechanism of symmetry breaking in a 3D model of a human epiblast, bioRxiv (preprint), 2018, vol. 21, p. 330704.

    Google Scholar 

  74. Smith, G.D., Swain, J.E., and Bormann, C.L., Microfluidics for gametes, embryos, and embryonic stem cells, Semin. Reprod. Med., 2011, vol. 29, no. 1, pp. 5–14.

    Article  CAS  PubMed  Google Scholar 

  75. Sozen, B., Amadei, G., Cox, A., et al., Self-assembly of embryonic and two extra-embryonic stem cell types into gastrulating embryo-like structures, Nat. Cell Biol., 2018, vol. 20, no. 8, pp. 979–989.

    Article  CAS  PubMed  Google Scholar 

  76. Steptoe, P.C. and Edwards, R.G., Birth after the reimplantation of a human embryo, Arch. Pathol. Lab. Med., 1978, vol. 116, no. 4, p. 321.

    Google Scholar 

  77. Tam, P.P.L., Postimplantation mouse development: whole embryo culture and micro- manipulation, Int. J. Dev. Biol., 1998, vol. 42, no. 7, pp. 895–902.

    CAS  PubMed  Google Scholar 

  78. Tao, T., Robichaud, A., Mercier, J., et al., Influence of group embryo culture strategies on the blastocyst development and pregnancy outcome, J. Assist. Reprod. Genet., 2013, vol. 30, no. 1, pp. 63–68.

    Article  PubMed  Google Scholar 

  79. Teklenburg, G., Salker, M., Molokhia, M., et al., Natural selection of human embryos: decidualizing endometrial stromal cells serve as sensors of embryo quality upon implantation, PLoS One, 2010, vol. 5, no. 4, pp. 2–7.

    Article  CAS  Google Scholar 

  80. Turco, M.Y., Gardner, L., Kay, R.G., et al., Trophoblast organoids as a model for maternal-fetal interactions during human placentation, Nature, 2018, vol. 564, no. 7735, pp. 263–281.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Vergaro, P., Tiscornia, G., Rodriguez, A., et al., Transcriptomic analysis of the interaction of choriocarcinoma spheroids with receptive vs. non-receptive endometrial epithelium cell lines: an in vitro model for human implantation, J. Assist. Reprod. Genet., 2019, vol. 36, no. 5, pp. 857–873.

    Article  PubMed  PubMed Central  Google Scholar 

  82. Vrij, E.J., Reimer, Y.S., Javier, F.A., et al., Self-organization of post-implantation-like embryonic tissues from blastoids, bioRxiv, 2019, p. 510396.

  83. Wang, H., Pila, F., Anderson, S., et al., A novel model of human implantation: 3d endometrium-like culture system to study attachment of human trophoblast (Jar) cell spheroids, Mol. Hum. Reprod., 2012, vol. 18, no. 1, pp. 33–43.

    Article  PubMed  CAS  Google Scholar 

  84. Wang, H., Bocca, S., Anderson, S., et al., Sex steroids regulate epithelial-stromal cell cross talk and trophoblast attachment invasion in a three-dimensional human endometrial culture system, Tissue Eng., Part C Methods, 2013, vol. 19, no. 9, pp. 676–687.

    Article  CAS  Google Scholar 

  85. Watkins, A.J., Platt, D., Papenbrock, T., et al., Mouse embryo culture induces changes in postnatal phenotype including raised systolic blood pressure, Proc. Natl. Acad. Sci. U. S. A., 2007, vol. 104, no. 13, pp. 5449–5454.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Ye, T.M., Pang, R.T.K., Leung, C.O.N., et al., Development and characterization of an endometrial tissue culture model for study of early implantation events, Fertil. Steril., 2012, vol. 98, no. 6, pp. 1581–1589.

    Article  CAS  PubMed  Google Scholar 

  87. Zhang, S., Chen, T., Chen, N., et al., Implantation initiation of self-assembled embryo-like structures generated using three types of mouse blastocyst-derived stem cells, Nat. Commun., 2019, vol. 10, no. 1.

  88. Zheng, Y., Xue, X., Shao, Y., et al., Controlled modelling of human epiblast and amnion development using stem cells, Nature, 2019, vol. 573, no. 7774, pp. 421–425.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Funding

This research was funded by the IDB RAS Government program of basic research no. 0108-2019-0004. 2020.

Author information

Authors and Affiliations

Authors

Contributions

L.Sh. Izmailova and E.A. Vorotelyak wrote the review text. E.A. Vorotelyak and A.V. Vasiliev edited the article.

Corresponding author

Correspondence to L. Sh. Izmailova.

Ethics declarations

The authors declare that they have no conflict of interest. This article does not contain any studies involving animals or human participants performed by any of the authors.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Izmailova, L.S., Vorotelyak, E.A. & Vasiliev, A.V. In Vitro Modeling of the Early Development of Mouse and Human Embryos. Russ J Dev Biol 51, 271–282 (2020). https://doi.org/10.1134/S1062360420050045

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S1062360420050045

Keywords:

Navigation