Human embryo research and the 14-day rule

Pera, Martin F.

doi:10.1242/dev.151191

Cited by 69 publications

(43 citation statements)

References 16 publications

(11 reference statements)

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“…Although recent technical advances have made it possible to image post implantation mouse embryos at cellular resolution (42), ethical challenges make it impossible to perform similar studies in a developing human embryo (43,44). Thus, gastruloids offer a unique tool to investigate human gastrulation.…”

Section: Discussionmentioning

confidence: 99%

Dissecting the dynamics of signaling events in the BMP, WNT, and NODAL cascade during self-organized fate patterning in human gastruloids

Chhabra

Liu

Goh

et al. 2018

Preprint

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During gastrulation, the pluripotent epiblast is patterned into the three germ layers, which form the embryo proper. This patterning requires a signaling cascade involving the BMP, WNT and NODAL pathways; however, how these pathways regulate one another in space and time to generate cell-fate patterns remains unknown. Using a human gastruloid model, we show that BMP signaling initiates a wave of WNT signaling, which, in turn, initiates a wave of NODAL signaling. While WNT propagation depends on continuous BMP activity, NODAL propagates independently of upstream signals. We further show that the duration of BMP signaling determines the position of mesodermal differentiation while WNT and NODAL synergize to achieve maximal differentiation. The waves of both WNT and NODAL signaling activity extend farther into the colony than mesodermal differentiation. Combining dynamic measurements of signaling activity with mathematical modeling revealed that the formation of signaling waves is inconsistent with WNT and NODAL forming a stable spatial pattern in signaling activities, and the final signaling state is spatially homogeneous. Thus, dynamic events in the BMP, WNT, and NODAL signaling cascade, in the absence of a signaling gradient, have the potential to mediate epiblast patterning.

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Section: Discussionmentioning

confidence: 99%

Dissecting the dynamics of signaling events in the BMP, WNT, and NODAL cascade during self-organized fate patterning in human gastruloids

Chhabra

Liu

Goh

et al. 2018

Preprint

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“…Advances in culture conditions have also increased the accessibility of the study of IVF embryos. Recently, human embryos have been cultured in vitro in a matrix that has allowed them to develop for up to 12-13 days, approaching the legally permitted limit of 14 days in the UK and subsequently adopted in many other countries (Pera, 2017). Surprisingly, the embryos seem to undergo normal post-implantation morphogenesis, forming a proamniotic cavity in the absence of any maternal input, suggesting that the pattern of early development resides entirely within the embryo itself (Shahbazi et al, 2016;Deglincerti et al, 2016).…”

Section: Sperm Preparation Including Capacitationmentioning

confidence: 99%

Humanin vitrofertilisation and developmental biology: a mutually influential history

Johnson

2019

Development

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This article describes the origins and development of in vitro fertilisation (IVF) and how it was influenced by, and influenced, basic research in developmental biology. It describes the technical and social challenges that confronted the pioneers in this field of study, and the considerable progress that has been made since those early days. It also considers how IVF has contributed, and continues to contribute, to our understanding of early human development.

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“…The fourteen-day rule was established as a policy tool-by, for instance, the Warnock commission in the 1980s-to find a balance between enabling research and maintaining public trust (Cavaliere 2017). Day fourteen was considered appropriate, because it signifies the point of individuation at which the primitive streak appears and twinning and fusion is no longer possible (Pera 2017). Those in favour of an extension of the rule by a few days refer to new promising options for research.…”

Section: Conditions For Preclinical Gene Editing In Embryosmentioning

confidence: 99%

Designing Preclinical Studies in Germline Gene Editing: Scientific and Ethical Aspects

Nordgren

2019

Bioethical Inquiry

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Human germline gene editing is often debated in hypothetical terms: if it were safe and efficient, on what further conditions would it then be ethically acceptable? This paper takes another course. The key question is: how can scientists reduce uncertainty about safety and efficiency to a level that may justify initiation of first-time clinical trials? The only way to proceed is by well-designed preclinical studies. However, what kinds of investigation should preclinical studies include and what specific conditions should they satisfy in order to be considered well-designed? It is argued that multispecies and multigenerational animal studies are needed as well as human embryo editing without implantation. In order to be possible to translate to first-time clinical trials, animal studies need to satisfy strict conditions of validity. Moreover, embryo studies intended for translation to first-time clinical trials need to correspond to the animal studies in experimental design (with exception of implantation). Only in this way can uncertainty about risk for harm (safety) and prospect of benefit (efficiency) in first-time clinical trials be reduced to a modest level. If uncertainty is not reduced to such a level, first-time clinical trials in germline gene editing should not be initiated.

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Human embryo research and the 14-day rule

Cited by 69 publications

References 16 publications

Dissecting the dynamics of signaling events in the BMP, WNT, and NODAL cascade during self-organized fate patterning in human gastruloids

Dissecting the dynamics of signaling events in the BMP, WNT, and NODAL cascade during self-organized fate patterning in human gastruloids

Humanin vitrofertilisation and developmental biology: a mutually influential history

Designing Preclinical Studies in Germline Gene Editing: Scientific and Ethical Aspects

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