Stem Cell-Derived Gametes

Note: article descriptions are taken from abstracts/articles.

See also: briefing document – State of the Science for Generating Gametes from Pluripotent Stem Cells

Easley, C. A., Simerly, C. R., & Schatten, G. (2015). Gamete derivation from embryonic stem cells, induced pluripotent stem cells or somatic cell nuclear transfer-derived embryonic stem cells: state of the art. Reproduction, Fertility, and Development, 27, 89-92, doi: 10.1071/RD14317.

Generating gametes from pluripotent stem cells (PSCs) has many scientific justifications and several biomedical rationales. Here, we consider several strategies for deriving gametes from PSCs from mice and primates (human and non-human) and their anticipated strengths, challenges and limitations. Although the ‘Weismann barrier’, which separates the mortal somatic cell lineages from the potentially immortal germline, has long existed, breakthroughs first in mice and now in humans are artificially creating germ cells from somatic cells. Spermatozoa with full reproductive viability establishing multiple generations of seemingly normal offspring have been reported in mice and, in humans, haploid spermatids with correct parent-of-origin imprints have been obtained. Similar progress with making oocytes has been published using mouse PSCs differentiated in vitro into primordial germ cells, which are then cultured after xenografting reconstructed artificial ovaries. Progress in making human oocytes artificially is proving challenging. The usefulness of these artificial gametes, from assessing environmental exposure toxicity to optimising medical treatments to prevent negative off-target effects on fertility, may prove invaluable, as may basic discoveries on the fundamental mechanisms of gametogenesis.

Special November 1014 issue of the Journal of Medical Ethics (vol. 40, issue 11) on the ethics of stem cell derived gametes, in vitro reproduction, and genetic parenthood.

This special issue of the Journal incorporates a series of articles on ethical questions raised by stem cell-derived gametes (SCDGs), understood here as gametes or gamete-like cells created in the laboratory from human pluripotent stem cells. The series includes five original research papers covering a wide range of ethical questions: Robert Sparrow’s feature article sets out to stimulate debate on the possible use of SCDG technology to create multiple generations of human embryos in vitro (see page 725, Editor’s choice); César Palacios-González, John Harris and Giuseppe Testa develop and deploy an ethical framework for assessing research uses of SCDG technology and appraise a range of fertility treatments that it may enable (see page 752); Heidi Mertes distinguishes a number of accounts of genetic parenthood and explores their implications for possible clinical applications of SCDGs (see page 744); Timothy Murphy discusses the possible use of SCDG technology to enable same-sex couples to have genetically related children and challenges some assumptions that have underpinned ethical discussions of this topic to date (see page 762); and Anna Smajdor and Daniela Cutas explore a number of ethical and legal questions raised by the possible use of SCDGs to create a person’s genetic child without her consent (see page 748). This Concise Argument focuses on Sparrow’s feature article and accompanying responses.

The concise argument

Stem-cell derived gametes

Easley, C. A., Latova, D. R., Simerly, C. R., & Schatten , G. (2014). Adult somatic cells to the rescue: nuclear reprogramming and the dispensability of gonadal germ cells. Fertility and Sterility, 101(1), 14-19, doi:10.1016/j.fertnstert.2013.11.025.

Recent advances in pluripotent stem cell differentiation and the generation of patient-specific, induced pluripotent stem cells indicate that stem cell replacement therapies or in vitro differentiation followed by IVF may be on the horizon. Here we discuss these recent advances, their relevance to treating male-factor and female-factor infertility, and what experimental procedures must be carried out in animal models before these exciting new treatments can be used in a clinical setting. The goal of this research is to generate functional gametes from no greater starting material than a mere skin biopsy.