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Do Pluripotent Stem Cells Offer a New Path to Reproduction?

Published online by Cambridge University Press:  30 January 2023

Audrey R. Chapman*
Division of Public Health Law and Bioethics, University of Connecticut, Farmington, CT, USA


The ability of pluripotent stem to develop into any of the cell types in the human body has meant that it was only a matter of time before scientists would try to transform them into human gametes. Up to now though it has not been possible to do so. Nevertheless a 2016 book written by Henry Greely speculated that in twenty to forty years most people in developed countries will cease reproduction through sex, using sex exclusively for pleasure, and instead will rely on reproduction through pluripotent stem cell-derived gametes. This paper will offer a different perspective. After describing the process through which human pluripotent stem cells might eventually be coaxed into gametes, it will show why the use of pluripotent stem cell-derived gametes for reproductive purposes would present significant safety, ethical, and regulatory challenges.

© 2023 The Author(s)

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1 Henry T. Greeley, The End of Sex and the Future of Human Reproduction (2016).

2 For more on the development of human embryonic stem cells and the controversy generated see A.R. Chapman, The Ethical Challenges of the Stem Cell Revolution (Newcastle upon Tyne, UK: Cambridge Scholars Publishing, 2020), Chapter 1.

3 L.C. Laurent et al., Dynamic Changes in the Copy Number of Pluripotency and Cell Proliferation Genes in Human ESCs and iPSCs During Reprogramming and Time in Culture, Cell Stem Cell 106-18 (2011); Liang & Y. Zhang, Genetic and Epigenetic Variations in iPSCs During Reprogramming and Time in Culture: Potential Causes and Implications for Applications, Cell Stem Cell 149-59 (2013).

4 Greeley, supra note 1, at 127.

5 Hinxton Group, Consensus Statement: Science, Ethics and Policy Challenges of Pluripotent Stem Cell-Derived Gametes 2 (2008)

6 Inmaculada de Melo‐Martín: Rethinking Reprogenetics: Enhancing Ethical Analysis of Reprogenetic Technologies 170 (2016).

7 Inmaculada Moreno et al., Artificial Gametes from Stem Cells, 33 CERM (2015).

8 Junaid Kashir et al., Viability Assessment for Artificial Gametes: The Need for Biomarkers of Functional Competency, Biology of Reproduction 1 (2012).

9 Anna Smajdor & Daniella Cutas, Artificial Gametes, Nuffield Council on Bioethics, 1, 9 (2016)

10 Kashir et al., supra note 8, at 3.

11 Greely, supra note 1, at 150-52.

12 Sonia M. Suter, The Tyranny of Choice: Reproductive Selection in the Future, 5 J. Law Biosci. 262, 265 (2016).

13 David Cyranoski, Rudimentary Egg and Sperm Cells Made from Stem Cells, Nature 1, 2 (2014).

14 David Cyranoski, Mouse eggs made from skin cells in a dish, Nature (2016).

15 Orie Hikabe et al., Reconstitution in vitro of the entire cycle of the mouse female germ line, Nature 299-303 (2016).

16 Takashi Yoshino et al., Generation of ovarian follicles from mouse pluripotent stem cells, Sci, July 2021 at 282-90.

17 Sujittra Khampang et al., Blastocyst Developed after Fertilisation with Invitro Spermatids from non-Human Primate Embryonic Stem Cells, 2 Fertility & Sterility Sci., 365, 366 (2021).

18 Naoko Irie et al., SOX17 Is a Critical Specifier of Human Primordial Cell Fate, 160, Cell 253, 253 (2015); D. Cyranoski, Rudimentary Egg and Sperm Cells Made from Stem Cells, Nature, (Dec. 24, 2014)

19 C. Yamashirobuta et al., Generation of Human Oogonia from Induced Pluripotent Stem Cells in vitro, Sci, Oct. 2018, at 356.

20 Smajdor & Cutas, supra note 9, at 12.

21 Sonia M. Suter, In Vitro Gametogenesis: Just Another Way to Have a Baby, 3 J. of L. & the Biosciences 87, 89 (2016).

22 Intl Commn on the Clinical Use of Hum. Germline Genome Editing et al., Heritable Human Genome Editing 3 (2020).

23 Suter, supra note 21, at 97-98.

24 Greely, supra note 1, at 218-222.

25 W. Dondorp & G. De Wert, Innovative reproductive technologies: risks and responsibilities, 26 Human Reproduction 1604, 1605 (2011).

26 Jennifer Couzin-Frankel, Unanswered Questions Surround Baby Born to Three Parents, News, Science (Sept. 27, 2016),

27 de Melo-Martin, supra note 6, at 265.

28 Amander T. Clark et. al., Human embryo research, stem cell-derived embryo models and in vitro gametogenesis: Considerations leading to the revised ISSCR guidelines, 16 Stem Cell Reports 1416, 1421 (2021).

29 Id. at 1421.

30 Id. at 1422.

31 Parts of this section of the paper are based on Chapter 7 in Chapman, supra note 2, at 149-69.

32 I. Glenn Cohen, George Daley & Eli Adashi, Disruptive Reproductive Technologies, 9 Sci. Transl. Med. (2017).

33 Ronald Green, The Human Embryo Research Debates: Bioethics in the Vortex of Controversy 79.

34 Annalien Bredenoord & Insoo Hyun, Ethics of Stem Cell-derived Gametes Made in a Dish: Fertility for Everyone? 9 EMBO Mol. Med. 396, 396 (2017).

35 Guido de Wert et al., Responsible Innovation in Human Germline Gene Editing: Background Document to the Recommendations of ESHG and ESHRE, 26 Eur. J. of Human. Gen. 450, 459 (2018).

36 Greely, supra note 1, at 133.

37 Id. at 238-40.

38 de Melo-Martin, supra note 6, at 15.

39 Commission on Human Gene Editing, supra note 22.

40 Greely, supra note 1, at 228.

41 Smajdor & Cutas, supra note 9.

42 Clark et al., supra note 27, at 6-7.

43 Id. at 6.

44 Eli Adashi et al., Stem Cell-Derived Human Gametes: The Public Engagement Imperative, 25 Trends in Mol. Med. 165, 165-67 (2019).

45 Clark et al., supra note 28, at 8.