DOCSLIB.ORG

Synthetic Human Embryology: Towards a Quantitative Future

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Synthetic Human Embryology: Towards a Quantitative Future Available online at www.sciencedirect.com ScienceDirect Synthetic human embryology: towards a quantitative future 1 2,3,4 Yue Shao and Jianping Fu Study of early human embryo development is essential for interest, as it is not only linked to reproductive health, advancing reproductive and regenerative medicine. Traditional but is also key to tissue engineering and regenerative human embryological studies rely on embryonic tissue medicine. Despite its scientific and clinical significance, specimens, which are difficult to acquire due to technical human embryo development remains largely mysterious. challenges and ethical restrictions. The availability of human Most of our knowledge about human development stem cells with developmental potentials comparable to pre- comes from limited histological specimens and medical implantation and peri-implantation human embryonic and images, preventing detailed understanding of human extraembryonic cells, together with properly engineered in vitro development. culture environments, allow for the first time researchers to in vitro generate self-organized multicellular structures that Although recent success in prolonging in vitro culture of in vivo mimic the structural and molecular features of their human embryo has generated new insights on human counterparts. The development of these stem cell-based, development [1–3], it is limited to a narrow time window synthetic human embryo models offers a paradigm-shifting due to ethical restrictions, namely, the 14-day rule [4], experimental system for quantitative measurements and prohibiting studies of post-implantation developmental perturbations of multicellular development, critical for stages such as gastrulation, neurulation, and beyond. advancing human embryology and reproductive and While in vitro culture of mouse and non-human primate regenerative medicine without using intact human embryos. embryos are not subject to this ethical restriction and thereby have enabled studies of peri-gastrulation devel- Addresses opment [5–9], clear evidence of interspecies divergence 1 Institute of Biomechanics and Medical Engineering, Department of between humans and mice [10,11] or non-human Engineering Mechanics, School of Aerospace Engineering, Tsinghua primates [3,12] calls for caution when extrapolating University, Beijing 100084, China 2 Department of Mechanical Engineering, University of Michigan, Ann knowledge from other mammals to humans. Further- Arbor, MI 48109, USA more, the limited availability of mammalian embryos, 3 Department of Cell and Developmental Biology, University of Michigan especially from non-human primates, prevents large-scale Medical School, Ann Arbor, MI 48109, USA 4 genetic studies or screens. Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, 48109, USA Recently, several groups, ours included, have success- Corresponding authors: fully reconstructed human embryogenic events in vitro Shao, Yue ([email protected]), Fu, Jianping ([email protected]) using human pluripotent stem cells (hPSC), an unlim- ited cell source with developmental potential matching Current Opinion in Genetics & Development 2020, 63:30–35 that of the pluripotent epiblast in the peri-implantation human embryo. By creating properly engineered culture This review comes from a themed issue on Dev. mechanisms, pat- environments, hPSC have now been applied to create terning and evolution multicellular structures to model the human amniotic sac Edited by Richard W Carthew and Amy Shyer formation, gastrulation, and neurulation. These stem cell-based human embryo models form the basis of the emerging field of synthetic human embryology, https://doi.org/10.1016/j.gde.2020.02.013 wherein different aspects of human embryo develop- in vitro 0959-437X/ã 2020 Elsevier Ltd. All rights reserved. ment are recreated and studied in a controllable and quantitative manner. Besides as an integrative area combining stem cell and developmental biology and human embryology, the advances in synthetic human embryology now have a new edge. By merging with designer bioengineering technologies and computational Introduction modeling, it is now possible to quantitatively control in vitro For centuries, the development of the human embryo has dynamic developmental niche and recapitulate in silico attracted great interest, especially on how it could give intricate developmental patterning . In this rise to the shape, size, function, and intelligence that review, we summarize the progress of this emerging make humans unique in the Mammalia class. Human field and its rapid advancement towards a quantitative embryo development also elicits significant clinical future. Current Opinion in Genetics & Development 2020, 63:30–35 www.sciencedirect.com Synthetic human embryology Shao and Fu 31 Models of human amniotic sac development including the specification of primordial germ cells. Upon implantation, the first developmental milestone of The microfluidic amniotic sac model is compatible with the human embryo is the formation of the asymmetric, live imaging, thus allowing tracking developmental lumenal amniotic sac from the epiblast of the human signaling dynamics. Given its controllability and scal- blastocyst. The amniotic sac is enveloped by the squa- ability, the microfluidic amniotic sac model could assist mous amniotic ectoderm at the dorsal pole and the in high-throughput drug and toxicity screens. Leverag- columnar epiblast at the ventral pole, respectively. The ing bioengineering tools for scalable tissue patterning, development of the amniotic sac is initiated by an apical another amniotic microtissue array system was recently lumen formation in the initial ball of pluripotent epiblast, reported [21], providing another promising platform for followed by patterning of the amniotic ectoderm at its high-throughput toxicity screens. dorsal pole [13] (Figure 1). Being an embryogenic event too early to detect, the development of the amniotic sac in Models of human gastrulation humans has been inaccessible for study until very After the amniotic sac formation, gastrulation is the next recently. Two recent studies report that hPSC have an developmental milestone. Gastrulation is initiated by the intrinsic lumenogenic property consistent with that of the formation of the primitive streak, culminating in the peri-implantation epiblast in vivo [2,14]. A hierarchical delineation of the three germ layers. The first human lumenogenic program in hPSC was further revealed, gastrulation model, termed ‘gastruloid’, was developed by mediated by actomyosin tension and driven by fusion culturing hPSC on 2D adhesive micropatterns of various of multiple pre-formed extracellular lumens or intracel- sizes. Treatments of 2D hPSC colonies with BMP4 lular apicosomes [15]. Importantly, such a ‘vesicle-fusion’ resulted in the emergence of concentric regions expres- mechanism of lumenogenesis was recently shown in both sing SOX2, T, SOX17, and CDX2, from colony center to mouse and human embryos [16,17]. Lumenal, pluripotent edge, mimicking the development of the three germ epithelial sacs of different shapes have also been gener- layers as well as the trophectoderm [22 ,23]. However, ated by culturing hPSC onto 2D culture surfaces contain- the gastruloid bypasses a few essential steps of gastrula- ing microscale grooves or trenches [14]. tion, namely, the formation of the primitive streak and its organizer. By replacing exogenous BMP4 with WNT3A, To recapitulate amniotic ectoderm development, two a morphologically distinguishable primitive streak-like culture systems were developed recently with tunable structure develops next to SOX2+ cells in the gastruloid mechanical stiffness of the culture environment [18 ,19 ]. [24 ]. Modulation of ACTIVIN-NODAL signaling in this Using both systems, a threshold of mechanical stiffness of streak model showed biased induction of posterior versus the culture environment was shown to control symmetry anterior primitive streak-like structures, as reflected by breaking of spherical lumenal hPSC tissues, resulting in differential SNAIL expression. Importantly, anterior prim- spontaneous differentiation of hPSC into squamous amni- itive streak-like structure induced in the model is GSC+, an otic cells and the formation of an asymmetric amniotic organizer marker. When such anterior primitive streak-like sac-like structure. Such a mechanical cell fate switch for structure was grafted into host chick embryos, it induced a amniotic differentiation of hPSC provides a potential secondary axis and neural tissue, confirming its role as an explanation for the absence of extraembryonic BMP organizer [24 ]. sources adjacent to the prospective amniotic ectoderm in vivo [13]. Amniogenic differentiation of hPSC requires Although 2D human gastruloid models provide trackable endogenous BMP-SMAD signaling [18 ]. By adjusting systems to study human gastrulation, they still deviate the initial cell number within each hPSC colony, syn- significantly from the actual human embryo in term of 3D thetic human amniotic sac model was created that not topology. To address this limitation, lumenal, pluripotent only resemble post-implantation amniotic sac develop- epithelial tissues formed by hPSC have recently been ment, but sequentially exhibit gastrulation-like features utilized for modeling human gastrulation [25 ]. With [19 ]. To date, this synthetic amniotic sac model remains precisely controlled, uniform BMP4 treatment, the 3D the only system that can recapitulate spontaneous
Load more

Recommended publications
  • 3 Embryology and Development
    BIOL 6505 − INTRODUCTION TO FETAL MEDICINE 3. EMBRYOLOGY AND DEVELOPMENT Arlet G. Kurkchubasche, M.D. INTRODUCTION Embryology – the field of study that pertains to the developing organism/human Basic embryology –usually taught in the chronologic sequence of events. These events are the basis for understanding the congenital anomalies that we encounter in the fetus, and help explain the relationships to other organ system concerns. Below is a synopsis of some of the critical steps in embryogenesis from the anatomic rather than molecular basis. These concepts will be more intuitive and evident in conjunction with diagrams and animated sequences. This text is a synopsis of material provided in Langman’s Medical Embryology, 9th ed. First week – ovulation to fertilization to implantation Fertilization restores 1) the diploid number of chromosomes, 2) determines the chromosomal sex and 3) initiates cleavage. Cleavage of the fertilized ovum results in mitotic divisions generating blastomeres that form a 16-cell morula. The dense morula develops a central cavity and now forms the blastocyst, which restructures into 2 components. The inner cell mass forms the embryoblast and outer cell mass the trophoblast. Consequences for fetal management: Variances in cleavage, i.e. splitting of the zygote at various stages/locations - leads to monozygotic twinning with various relationships of the fetal membranes. Cleavage at later weeks will lead to conjoined twinning. Second week: the week of twos – marked by bilaminar germ disc formation. Commences with blastocyst partially embedded in endometrial stroma Trophoblast forms – 1) cytotrophoblast – mitotic cells that coalesce to form 2) syncytiotrophoblast – erodes into maternal tissues, forms lacunae which are critical to development of the uteroplacental circulation.
    [Show full text]
  • Te2, Part Iii
    TERMINOLOGIA EMBRYOLOGICA Second Edition International Embryological Terminology FIPAT The Federative International Programme for Anatomical Terminology A programme of the International Federation of Associations of Anatomists (IFAA) TE2, PART III Contents Caput V: Organogenesis Chapter 5: Organogenesis (continued) Systema respiratorium Respiratory system Systema urinarium Urinary system Systemata genitalia Genital systems Coeloma Coelom Glandulae endocrinae Endocrine glands Systema cardiovasculare Cardiovascular system Systema lymphoideum Lymphoid system Bibliographic Reference Citation: FIPAT. Terminologia Embryologica. 2nd ed. FIPAT.library.dal.ca. Federative International Programme for Anatomical Terminology, February 2017 Published pending approval by the General Assembly at the next Congress of IFAA (2019) Creative Commons License: The publication of Terminologia Embryologica is under a Creative Commons Attribution-NoDerivatives 4.0 International (CC BY-ND 4.0) license The individual terms in this terminology are within the public domain. Statements about terms being part of this international standard terminology should use the above bibliographic reference to cite this terminology. The unaltered PDF files of this terminology may be freely copied and distributed by users. IFAA member societies are authorized to publish translations of this terminology. Authors of other works that might be considered derivative should write to the Chair of FIPAT for permission to publish a derivative work. Caput V: ORGANOGENESIS Chapter 5: ORGANOGENESIS
    [Show full text]
  • The Rotated Hypoblast of the Chicken Embryo Does Not Initiate an Ectopic Axis in the Epiblast
    Proc. Natl. Acad. Sci. USA Vol. 92, pp. 10733-10737, November 1995 Developmental Biology The rotated hypoblast of the chicken embryo does not initiate an ectopic axis in the epiblast ODED KHANER Department of Cell and Animal Biology, The Hebrew University, Jerusalem, Israel 91904 Communicated by John Gerhart, University of California, Berkeley, CA, July 14, 1995 ABSTRACT In the amniotes, two unique layers of cells, of the hypoblast and that the orientation of the streak and axis the epiblast and the hypoblast, constitute the embryo at the can be predicted from the polarity of the stage XIII epiblast. blastula stage. All the tissues of the adult will derive from the Still it was thought that the polarity of the epiblast is sufficient epiblast, whereas hypoblast cells will form extraembryonic for axial development in experimental situations, although in yolk sac endoderm. During gastrulation, the endoderm and normal development the polarity of the hypoblast is dominant the mesoderm of the embryo arise from the primitive streak, (5, 6). These reports (1-3, 5, 6), taken together, would imply which is an epiblast structure through which cells enter the that cells of the hypoblast not only have the ability to change interior. Previous investigations by others have led to the the fate of competent cells in the epiblast to initiate an ectopic conclusion that the avian hypoblast, when rotated with regard axis, but also have the ability to repress the formation of the to the epiblast, has inductive properties that can change the original axis in committed cells of the epiblast. At the same fate of competent cells in the epiblast to form an ectopic time, the results showed that the epiblast is not wholly depen- embryonic axis.
    [Show full text]
  • Comparing the Differentiation Potential of Brachyury+ Mesodermal Cells
    bioRxiv preprint doi: https://doi.org/10.1101/239913; this version posted December 26, 2017. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC 4.0 International license. 1 of 44 + 1 Comparing the differentiation potential of Brachyury mesodermal 2 cells generated from 3-D and 2-D culture systems 3 Jing Zhou 1, Antonius Plagge 1 and Patricia Murray 1,* 4 1 Institute of Translational Medicine, University of Liverpool, Liverpool L69 3BX, UK; E-mails: 5 [email protected] (J.Z.); [email protected] (A.P.); [email protected] 6 (P.M.) 7 * Correspondence: [email protected] 8 Abstract 9 Mesodermal populations can be generated in vitro from mouse embryonic stem cells (mESCs) using 10 three-dimensional (3-D) aggregates called embryoid bodies or two-dimensional (2-D) monolayer 11 culture systems. Here, we investigated whether Brachyury-expressing mesodermal cells generated 12 using 3-D or 2-D culture systems are equivalent, or instead, have different properties. Using a 13 Brachyury-GFP/E2-Crimson reporter mESC line, we isolated Brachyury-GFP+ mesoderm cells using 14 flow-activated cell sorting and compared their gene expression profiles and ex vivo differentiation 15 patterns. Quantitative RT-PCR analysis showed significant up-regulation of Cdx2, Foxf1 and Hoxb1 in 16 the Brachyury-GFP+ cells isolated from the 3-D system compared with those isolated from the 2-D 17 system.
    [Show full text]
  • Gastrulation
    Embryology of the spine and spinal cord Andrea Rossi, MD Neuroradiology Unit Istituto Giannina Gaslini Hospital Genoa, Italy [email protected] LEARNING OBJECTIVES: LEARNING OBJECTIVES: 1) To understand the basics of spinal 1) To understand the basics of spinal cord development cord development 2) To understand the general rules of the 2) To understand the general rules of the development of the spine development of the spine 3) To understand the peculiar variations 3) To understand the peculiar variations to the normal spine plan that occur at to the normal spine plan that occur at the CVJ the CVJ Summary of week 1 Week 2-3 GASTRULATION "It is not birth, marriage, or death, but gastrulation, which is truly the most important time in your life." Lewis Wolpert (1986) Gastrulation Conversion of the embryonic disk from a bilaminar to a trilaminar arrangement and establishment of the notochord The three primary germ layers are established The basic body plan is established, including the physical construction of the rudimentary primary body axes As a result of the movements of gastrulation, cells are brought into new positions, allowing them to interact with cells that were initially not near them. This paves the way for inductive interactions, which are the hallmark of neurulation and organogenesis Day 16 H E Day 15 Dorsal view of a 0.4 mm embryo BILAMINAR DISK CRANIAL Epiblast faces the amniotic sac node Hypoblast Primitive pit (primitive endoderm) faces the yolk sac Primitive streak CAUDAL Prospective notochordal cells Dias Dias During
    [Show full text]
  • Massive Subchorionic Haemorrhage: a Rare Case Report Associated with Secondary PPH Due to Uterine Artery Pseudoaneurysm
    International Journal of Reproduction, Contraception, Obstetrics and Gynecology Arumaikannu J et al. Int J Reprod Contracept Obstet Gynecol. 2017 Oct;6(10):4723-4726 www.ijrcog.org pISSN 2320-1770 | eISSN 2320-1789 DOI: http://dx.doi.org/10.18203/2320-1770.ijrcog20174475 Case Report Massive subchorionic haemorrhage: a rare case report associated with secondary PPH due to uterine artery pseudoaneurysm J. Arumaikannu*, S. Usha Rani, T. S. Aarifa Thasleem Institute of Obstetrics and Gynecology, Egmore, Chennai, Tamil Nadu, India Received: 08 August 2017 Accepted: 04 September 2017 *Correspondence: Dr. J. Arumaikannu, E-mail: [email protected] Copyright: © the author(s), publisher and licensee Medip Academy. This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. ABSTRACT Massive subchorionic hemorrhage is a rare but serious condition in pregnancy in which a large amount of blood, mainly maternal collects between the uterine wall and the chorionic membrane and may leak through the cervical canal. Although many associations have been reported, an underlying etiology has not been elucidated. Association of massive subchorionic hemorrhage with thrombophilias have been reported in few articles. We are reporting a case of massive subchorionic hemorrhage presented at 13 weeks of gestation associated with secondary post-partum hemorrhage due to uterine artery pseudoaneurysm. Keywords: Massive subchorionic haemorrhage, Secondary PPH, Uterine artery pseudoaneurysm INTRODUCTION hemorrhage in the second trimester may also compromise maternal health.2,3 During pregnancy, minor degrees of haemorrhage on the chorionic plate surface of the placenta are commonly A subchorionic hemorrhage can be considered large or identified on ultrasound assessment.
    [Show full text]
  • A Guide to Obstetrical Coding Production of This Document Is Made Possible by Financial Contributions from Health Canada and Provincial and Territorial Governments
    ICD-10-CA | CCI A Guide to Obstetrical Coding Production of this document is made possible by financial contributions from Health Canada and provincial and territorial governments. The views expressed herein do not necessarily represent the views of Health Canada or any provincial or territorial government. Unless otherwise indicated, this product uses data provided by Canada’s provinces and territories. All rights reserved. The contents of this publication may be reproduced unaltered, in whole or in part and by any means, solely for non-commercial purposes, provided that the Canadian Institute for Health Information is properly and fully acknowledged as the copyright owner. Any reproduction or use of this publication or its contents for any commercial purpose requires the prior written authorization of the Canadian Institute for Health Information. Reproduction or use that suggests endorsement by, or affiliation with, the Canadian Institute for Health Information is prohibited. For permission or information, please contact CIHI: Canadian Institute for Health Information 495 Richmond Road, Suite 600 Ottawa, Ontario K2A 4H6 Phone: 613-241-7860 Fax: 613-241-8120 www.cihi.ca [email protected] © 2018 Canadian Institute for Health Information Cette publication est aussi disponible en français sous le titre Guide de codification des données en obstétrique. Table of contents About CIHI ................................................................................................................................. 6 Chapter 1: Introduction ..............................................................................................................
    [Show full text]
  • Drug Use and Pregnancy
    Rochester Institute of Technology RIT Scholar Works Theses 7-28-1999 Drug use and pregnancy Kimberly Klapmust Follow this and additional works at: https://scholarworks.rit.edu/theses Recommended Citation Klapmust, Kimberly, "Drug use and pregnancy" (1999). Thesis. Rochester Institute of Technology. Accessed from This Thesis is brought to you for free and open access by RIT Scholar Works. It has been accepted for inclusion in Theses by an authorized administrator of RIT Scholar Works. For more information, please contact [email protected]. ROCHESTER INSTITUTE OF TECHNOLOGY A Thesis Submitted to the Faculty of The College of Imaging Arts and Sciences In Candidacy for the Degree of MASTER OF FINE ARTS Drug Use and Pregnancy by Kimberly A. Klapmust July 28, 1999 Approvals Adviser: Robert Wabnitz Date: Associate Adviser. Dr. Nancy Wanek ~)14 Date: \\.\,, c Associate Advisor: Glen Hintz Date ]I-I, zJ Cf9 I 7 Department ChaiIWrson: _ Dale: 1//17._/c; '1 I, , hereby deny permission to the Wallace Memorial library of RIT to reproduce my thesis in whole or in part. Any reproduction will not be for commercial use or profit. INTRODUCTION Human development is a remarkably complex process whereby the union of two small cells can after a period of time give rise to a new human being, complete with vital organs, bones, muscles, nerves, blood vessels, and much more. Considering the intricacy of the developmental process, it is indeed miraculous that most babies are born healthy. Some children, however, are born with abnormalities. Environmental agents, such as drugs, are responsible for some of these abnormalities.
    [Show full text]
  • Stages of Embryonic Development of the Zebrafish
    DEVELOPMENTAL DYNAMICS 2032553’10 (1995) Stages of Embryonic Development of the Zebrafish CHARLES B. KIMMEL, WILLIAM W. BALLARD, SETH R. KIMMEL, BONNIE ULLMANN, AND THOMAS F. SCHILLING Institute of Neuroscience, University of Oregon, Eugene, Oregon 97403-1254 (C.B.K., S.R.K., B.U., T.F.S.); Department of Biology, Dartmouth College, Hanover, NH 03755 (W.W.B.) ABSTRACT We describe a series of stages for Segmentation Period (10-24 h) 274 development of the embryo of the zebrafish, Danio (Brachydanio) rerio. We define seven broad peri- Pharyngula Period (24-48 h) 285 ods of embryogenesis-the zygote, cleavage, blas- Hatching Period (48-72 h) 298 tula, gastrula, segmentation, pharyngula, and hatching periods. These divisions highlight the Early Larval Period 303 changing spectrum of major developmental pro- Acknowledgments 303 cesses that occur during the first 3 days after fer- tilization, and we review some of what is known Glossary 303 about morphogenesis and other significant events that occur during each of the periods. Stages sub- References 309 divide the periods. Stages are named, not num- INTRODUCTION bered as in most other series, providing for flexi- A staging series is a tool that provides accuracy in bility and continued evolution of the staging series developmental studies. This is because different em- as we learn more about development in this spe- bryos, even together within a single clutch, develop at cies. The stages, and their names, are based on slightly different rates. We have seen asynchrony ap- morphological features, generally readily identi- pearing in the development of zebrafish, Danio fied by examination of the live embryo with the (Brachydanio) rerio, embryos fertilized simultaneously dissecting stereomicroscope.
    [Show full text]
  • Understanding Paraxial Mesoderm Development and Sclerotome Specification for Skeletal Repair Shoichiro Tani 1,2, Ung-Il Chung2,3, Shinsuke Ohba4 and Hironori Hojo2,3
    Tani et al. Experimental & Molecular Medicine (2020) 52:1166–1177 https://doi.org/10.1038/s12276-020-0482-1 Experimental & Molecular Medicine REVIEW ARTICLE Open Access Understanding paraxial mesoderm development and sclerotome specification for skeletal repair Shoichiro Tani 1,2, Ung-il Chung2,3, Shinsuke Ohba4 and Hironori Hojo2,3 Abstract Pluripotent stem cells (PSCs) are attractive regenerative therapy tools for skeletal tissues. However, a deep understanding of skeletal development is required in order to model this development with PSCs, and for the application of PSCs in clinical settings. Skeletal tissues originate from three types of cell populations: the paraxial mesoderm, lateral plate mesoderm, and neural crest. The paraxial mesoderm gives rise to the sclerotome mainly through somitogenesis. In this process, key developmental processes, including initiation of the segmentation clock, formation of the determination front, and the mesenchymal–epithelial transition, are sequentially coordinated. The sclerotome further forms vertebral columns and contributes to various other tissues, such as tendons, vessels (including the dorsal aorta), and even meninges. To understand the molecular mechanisms underlying these developmental processes, extensive studies have been conducted. These studies have demonstrated that a gradient of activities involving multiple signaling pathways specify the embryonic axis and induce cell-type-specific master transcription factors in a spatiotemporal manner. Moreover, applying the knowledge of mesoderm development, researchers have attempted to recapitulate the in vivo development processes in in vitro settings, using mouse and human PSCs. In this review, we summarize the state-of-the-art understanding of mesoderm development and in vitro modeling of mesoderm development using PSCs. We also discuss future perspectives on the use of PSCs to generate skeletal tissues for basic research and clinical applications.
    [Show full text]
  • The Law of Placenta
    The Law of Placenta Mathilde Cohent ABSTRACT: Of the forms of reproductive labor in which legal scholars have been interested, placenta, the organ developed during pregnancy, has been overlooked. As placenta becomes an object of value for a growing number of individuals, researchers, clinicians, biobanks, and biotech companies, among others, its cultural meaning is changing. At the same time, these various constituencies may be at odds. Some postpartum parents and their families want to repossess their placenta for personal use, while third parties use placentas for a variety of research, medical, and commercial purposes. This Article contributes to the scholarship on reproductive justice and agency by asking who should have access to placentas and under what conditions. The Article emphasizes the insufficient protection the law affords pregnant people wishing to decide what happens to their placenta. Generally considered clinical waste under federal and state law, placental tissue is sometimes made inaccessible to its producers on the ground that it is infectious at the same time as it is made available to third parties on the ground that placenta is discarded and de-identified tissue. Less privileged people who lack the ability to shop for obstetric and other pregnancy-related services that allow them to keep their placentas are at a disadvantage in this chain of supply and demand. While calling for further research on the modus operandi of placenta markets and how pregnant people think about them, this Article concludes that lawmakers should take steps to protect decision-making autonomy over placental labor and offers a range of proposals to operationalize this idea.
    [Show full text]
  • Cell Fate in the Early Mouse Embryo: Sorting out the Influence of Developmental History on Lineage Choice
    Reproductive BioMedicine Online (2011) 22, 521– 524 www.sciencedirect.com www.rbmonline.com COMMENTARY Cell fate in the early mouse embryo: sorting out the influence of developmental history on lineage choice Samantha A Morris Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, UK; University of Cambridge, Department of Physiology, Development and Neurobiology, Downing Street, Cambridge CB2 3DY, UK E-mail address: [email protected]. Abstract In early mouse embryos the first cell-fate decision segregates two cell populations: the outer trophectoderm (TE) and inner cell mass (ICM). Cells are primarily directed to the ICM in two waves of asymmetric division at the 8–16-cell and 16–32-cell stage transition – the first and second waves, respectively. The ICM then diverges to become epiblast (EPI) which will generate the embryo/fetus and extra-embryonic primitive endoderm (PE). Two recent studies have aimed to address the developmental origins of these lineages. Morris et al. (2010) found that first-wave-internalized cells mainly generate EPI, whereas later internalized cells pro- vide PE. This trend was not reflected in an independent study (Yamanaka et al., 2010). From direct comparison of both datasets, it becomes clear that the key difference lies in the proportions of cells internalized in the two waves, impacting greatly upon fate. When the majority of ICM is derived from only the first wave, both EPI and PE must differentiate from the available cells and no pattern is observed. Frequently though, closer parity exists between cells dividing asymmetrically in the first and second waves, revealing the influence of developmental history upon fate.
    [Show full text]