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Author(s): Helen ShenAuthor Affiliations:The labs growing human embryos for longer than ever before For two tense weeks in mid-2013, developmental biologist Magdalena Zernicka-Goetz was chasing a world record. She and [...], New techniques are providing unprecedented views into human development -- and raising ethical questions.New techniques are providing unprecedented views into human development -- and raising ethical questions.

This article explores' the plausibility of an argument against embryonic stem cell research based on what the regulations already say about research on pregnant women and fetuses. The center of the argument is the notion of vulnerability and whether such a concept is applicable to human embryos. It is argued that such an argument can be made plausible. The article concludes by responding to several important objections. Keywords: embryo., moral worth, regulations, research, vulnerability

Author(s): Marta N. Shahbazi [1]; Antonio Scialdone [2]; Natalia Skorupska [1]; Antonia Weberling [1]; Gaelle Recher [1]; Meng Zhu [1]; Agnieszka Jedrusik [1]; Liani G. Devito [3]; Laila Noli [3]; [...]

The metastatic spread of epithelial cancer cells from the primary tumor to distant organs mimics the cell migrations that occur during embryogenesis. Using gene expression profiling, we have found that the FOXC2 transcription factor, which is involved in specifying mesenchymal cell fate during embryogenesis, is associated with the metastatic capabilities of cancer cells. FOXC2 expression is required for the ability of murine mammary carcinoma cells to metastasize to the lung, and overexpression of FOXC2 enhances the metastatic ability of mouse mammary carcinoma cells. We show that FOXC2 expression is induced in cells undergoing epithelial-mesenchymal transitions (EMTs) triggered by a number of signals, including TGF-[beta]1 and several EMT-inducing transcription factors, such as Snail, Twist, and Goosecoid. FOXC2 specifically promotes mesenchymal differentiation during an EMT and may serve as a key mediator to orchestrate the mesenchymal component of the EMT program. Expression of FOXC2 is significantly correlated with the highly aggressive basal-like subtype of human breast cancers. These observations indicate that FOXC2 plays a central role in promoting invasion and metastasis and that it may prove to be a highly specific molecular marker for human basal-like breast cancers. epithelial-mesenchymal transition | embryogenesis | Twist and Snail

During human embryo implantation, trophectoderm mediates adhesion of the blastocyst to the uterine epithelium. The rapid growth of the embryo and invasion of the maternal tissue suggest adhesion-induced activation of the embryonal cells. We show here that ligation of trophinin, a homophilic cell adhesion molecule expressed on trophoblastic cells, induces tyrosine phosphorylation in trophinin-expressing trophoblastic HT-H cells. The phosphorylation could be induced in HT-H cells with the binding of trophinin-expressing cells or anti trophinin antibodies. Trophinin-dependent tyrosine phosphorylation was associated with actin reorganization. We also isolated trophinin-binding peptides from phage libraries. These peptides exhibited the consensus sequence GWRQ and seemed to reproduce the effects of trophinin-mediated cell adhesion. Upon binding of a GWRQ peptide, HT-H cells became highly proliferative and motile. HT-H cells expressed ErbB family receptors and bound EGF and heparin-binding EGF-like growth factor (HB-EGF), but ErbB family receptor phosphorylation in these cells required GWRQ. In the absence of GWRQ, trophinin interacted with the cytoplasmic protein bystin, which binds to ErbB4 and blocks its autophosphorylation. In HT-H cells, GWRQ peptide dissociated trophinin from bystin, and ErbB4 was activated. Culturing monkey blastocysts in the presence of the peptide increased total number and motility of the trophectoderm cells. These results suggest that trophinin-mediated cell adhesion functions as a molecular switch for trophectoderm activation in human embryo implantation. BYSL | ErbB4 | pregnancy | receptor tyrosine kinase | stem cells

ABSTRACT During the first 16 days after fertilization, the developing embryo has the capacity to separate into two genetically identical embryos, or monozygotic twins (triplets, etc.). Because of this capacity, [...]

A randomized controlled trial is designed to determine whether there are differences in the rates of pregnancy and delivery between women randomly assigned to undergo transfer of a single cleavage-stage embryo and those assigned to undergo transfer of a single blastocyst-stage embryo. The results show that the transfer of a single blastocyst-stage embryo significantly increases the likelihood of pregnancy and delivery as compared with transfer of a single cleavage-stage embryo.

In March 2004, the Assisted Human Reproduction (AHR) Act received Royal Assent. (1) The law includes an explicit prohibition on the creation of human embryos for research. Consequently, the only […]

In addressing bioethical issues at the beginning of human life, such as abortion, in vitro fertilization, and embryonic stem cell research, one primary concern regards establishing when a developing human embryo or fetus can be considered a person. Thomas Aquinas argues that an embryo or fetus is not a human person until its body is informed by a rational soul. Aquinas's explicit account of human embryogenesis has been generally rejected by contemporary scholars due to its dependence upon medieval biological data, which has been far surpassed by current scientific research. A number of scholars, however, have attempted to combine Aquinas's basic metaphysical account of human nature with current embryological data to develop a contemporary Thomistic account of a human person's beginning. In this article, I discuss two recent interpretations in which it is argued that a human person does not begin to exist until a fetus has developed a functioning cerebral cortex. Keywords: Aquinas, Donceel, embryo, Pasnau, person, soul

Two different discussions in John Rawls' A Theory of Justice lead naturally to a rather conservative position on the moral status of the human embryo. When discussing paternalism, he claims that the parties in the original position would seek to protect themselves in case they end up as incapacitated or undeveloped human beings when the veil of ignorance is lifted. Since human embryos are examples of such beings, the parties in the original position would seek to protect themselves from their embryonic stages onward. When discussing the basis of equality, Rawls claims that the parties in the original position would guarantee basic rights for all those with the capacity to take part in this original position. To guarantee the basic rights of infants and young children, he goes on to interpret this capacity as a 'potentiality that is ordinarily realized in due course.' Since human embryos have this potentiality, they too should have basic rights. Keywords: embryos, equality, moral status, potential, Rawls

The therapeutic use of nuclear transfer does not require the formation of a fetus but relies on the direct differentiation of functional cells in nature. A cloned human embryo would have little potential to develop into a healthy human being, as it would lack attributes that are essential to the beginning of normal human life.

The President George W. Bush's policy has severely curtailed opportunities for U.S. scientists to study the cell lines that have since been established, many of which have unique attributes or represent invaluable models of human disease. The science of human embryonic stem cells is in its infancy, and the current policies threaten to starve the field at a critical stage are discussed.

Introduction Embryonic stem cells are touted as a source of promising treatment for debilitating diseases such as Parkinsons, Alzheimers, diabetes, cardiovascular disease, and many others. (1) In order to exploit [...]

Byline: Pavel Gurevich (), Asher Elhayany (), Herzl Ben-Hur (), Moisey Moldavsky (), Sergio Szvalb (), Judit Zandbank (), David F. Schneider (), Itshak Zusman () Abstract: In our previous studies, we described the development of the secretory (mucosal) immune system (SIS) in human fetuses in the second trimester of pregnancy. In the present study, we examined the presence and distribution of components of this system in human embryos and early fetuses in the first trimester. An immunohistochemical study was performed on 17 embryos and 9 fetuses (4 to 12 wk of development) using antibodies against secretory component (SC), joining (J) chain, immunoglobulins (IgA, IgM, IgG), subsets of T and B lymphocytes, and macrophages. Cells positive for SC, J chain, and IgG were found in epithelial tissues from wk 4 of pregnancy. In the internal organs, such as the myocardium and endocardium, capillary endothelium, epithelium of the kidney tubules and some others, only J chain and immunoglobulins were seen. IgA was weakly reactive in tissues where SC and/or J chain were presented. IgM was very weak or absent. Among the cellular components of the SIS, only macrophages were seen in 4-wk-old embryos. CD3+ and CD20+ lymphocytes were found at wk 7 to 8. IgA- and IgM-positive lymphocytes appeared at the end of wk 9. The SIS is widespread in embryonic and early fetal periods and begins to function before the appearance of the common immune system in the developing organism. The first functional components of the SIS, such as IgG and IgA observed in this study, are most probably of maternal origin. Author Affiliation: () Laboratory of Experimental Medicine, Institute of Pathology, Assaf Harofeh Medical Center, 12B Hamada Street, Park Rabin, Rehovot 76100, Israel, IL () Central District, Clalit Health Services, Rishon Leziyon, Israel, IL () Department of Obstetrics and Gynecology, Assaf Harofeh Medical Center, Tserifin, Israel, IL () Department of Pathology, Rebecca Sieff Hospital, Safed, Israel, IL () Institute of Pathology, Assaf Harofeh Medical Center, Tserifin, Israel, IL () Koret School of Veterinary Medicine, Faculty of Agricultural, Food and Environmental Quality Sciences, The Hebrew University of Jerusalem, Box 12, Rehovot 76100, Israel, IL Article History: Received Date: 28/12/2001 Accepted Date: 14/03/2002

In August of last year, President Bush approved the use of federal funds to support research on a limited number of existing human embryonic stem cell lines. The decision met [...]

To determine the three-dimensional (3-D) shape of a live embryo is a technically challenging task. We show that reconstructions of live embryos can be done by collecting images from different viewing angles using a robotic macroscope, establishing point correspondences between these views by block matching, and using a new 3-D reconstruction algorithm that accommodates camera positioning errors. The algorithm assumes that the images are orthographic projections of the object and that the camera scaling factors are known. Point positions and camera errors are found simultaneously. Reconstructions of test objects and embryos show that meaningful reconstructions are possible only when camera positioning and alignment errors are accommodated since these errors can be substantial. Reconstructions of early-stage axolotl embryos were made from sets of 33 images. In a typical reconstruction, 781 points, each visible in at least three different views, were used to form 1511 triangles to represent the embryo surface. The resulting reconstruction had a mean radius of error of 0.27 pixels (1.1 [[micro]meter]). Mathematical properties of the reconstruction algorithm are identified and discussed. Index Terms - Block matching, camera error, embryos, morphometrics, multiview reconstruction, three-dimensional (3-D) reconstruction.

Recent evidence emerging from several laboratories, integrated with new data obtained by searching the genome databases, suggests that the area code hypothesis provides a good heuristic model for explaining the remarkable specificity of cell migration and tissue assembly that occurs throughout embryogenesis. The area code hypothesis proposes that cells assemble organisms, including their brains and nervous systems, with the aid of a molecular-addressing code that functions much like the country, area, regional, and local portions of the telephone dialing system. The complexity of the information required to code cells for the construction of entire organisms is so enormous that we assume that the code must make combinatorial use of members of large multigene families. Such a system would reuse the same receptors as molecular digits in various regions of the embryo, thus greatly reducing the total number of genes required. We present the hypothesis that members of the very large families of olfactory receptors and vomeronasal receptors fulfill the criteria proposed for area code molecules and could serve as the last digits in such a code. We discuss our evidence indicating that receptors of these families are expressed in many parts of developing embryos and suggest that they play a key functional role in cell recognition and targeting not only in the olfactory system but also throughout the brain and numerous other organs as they are assembled.

Two putative G protein-coupling regions of CXCR2 were mutated and their effects on ligand-activated signal transductions were characterized in stably transfected human embryonic kidney 293 cells. Results indicate that while ligand binding is retained in the D89N and BBXXB motif mutants, alternation of CXCR2 through the insertion of two isoleucine residues in the BBXXB motif prevents ligand-induced G protein-coupling, chemotaxis and calcium mobilization.

Potassium-chloride cotransporter isoform, KCC2, in stably transfected human embryonic kidney-293 cell lines, displays the basic transport features of a K-Cl cotransport system. By analyzing its functions, it has been observed that the expressed KCC2 protein exhibits a very high affinity for external Rb+(K+), Michaelis constant (Km)~5 mM. This suggest that aside from the maintenance of low neuronal Cl-, KCC2 may assist in buffering the external K+ concentration in the brain.

Studies of human embryonic kidney cells indicated that polyamines are potent agonists for the calcium-sensing receptor (CaR). CaR altered several cellular parameters such as inositol phosphate production, cytosolic free calcium and the activity of a nonselective cation channel. Activation of intracellular calcium transients was produced by spermine. External calcium and spermine both inhibited parathyroid hormone secretion. These results implied the significance of polyamines as effective agonists for the CaR and their role as neurotransmitters or neuromodulators.

The development of public policy on bioethical issues can be approached through substantive moral and philosophic reasoning, or through balancing perceived societal views as to what is ethically acceptable. The Human Embryo Research Panel had to apply the first approach to the question of the moral status of the preimplantation embryo. Only after concluding that the preimplantation embryo was not a full human subject could the panel consider the conditions under which embryo research was ethically acceptable, given a range of societal views, concerns, and interests. Key Words: embryo, federal regulations, moral status, public policy, research

Scientists must develop a new argument to convince Congress to fund embryo research. The Human Embryo Research Panel was created in 1994 to recommend which types of embryo research should be funded, but their recommendations have been ignored. This probably occurred because embryo research is linked to abortion. In January, 1996, Pres Clinton prohibited the use of federal funds for embryo research. Many people cannot accept creating embryos specifically for research because this would involve treating human embryos as commodities. However, they might accept research on spare embryos that were created during in vitro fertilization and other fertility treatments. A 1995 Congressional amendment to permit federal funding for research on spare embryos failed only because the vote was tied. By linking embryo research to research on infertility, scientists might have a better chance of gaining Congressional support.

One frequent argument in the debate over federal funding of human embryo research is the slippery slope argument. Slope arguments can be of several types: either logical, empirical or full (a combination of logical and empirical slope arguments, with an additional psychological premise). A full slope argument against human embryo research suggests that funding embryo research could undermine current protections for human subjects research, erode respect for persons with disabilities, and encourage eugenics practices. While the Panel commissioned by the National Institutes of Health to issue funding guidelines regarding human embryo research acknowledges some slippery slope concerns, the Panel's final report fails to address such concerns in any depth. Given this failure seriously to address these valid concerns, federal funding of embryo research should not proceed at this time. Key Words: embryo, human, slippery slope

A study was conducted on the expression of the nonclassical class I major histocompatibility complex molecule HLA-G throughout human preimplantation development from the oocyte to blastocyst stages. Results showed that HLA-G heavy and light chains are expressed at the mRNA and protein levels by some human oocytes and preimplantation embryos at each cleavage stage up to the blastocyst. The results suggest that HLA-G expression may have an important function in human embryo survival.