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Stem Cells in Reproductive Medicine
  • 3rd edition
  • Edited by Carlos Simón, Instituto Valenciano de Infertilidad, University of Valencia , Antonio Pellicer, Instituto Valenciano de Infertilidad, University of Valencia , Renee Reijo Pera, Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine
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Book description

Stem cell science has the potential to impact human reproductive medicine significantly – cutting edge technologies allow the production and regeneration of viable gametes from human stem cells offering potential to preciously infertile patients. Written by leading experts in the field Stem Cells in Reproductive Medicine brings together chapters on the genetics and epigenetics of both the male and female gametes as well as advice on the production and regeneration of gene cells in men and women, trophoblasts and endometrium from human embryonic and adult stem cells. Although focussing mainly on the practical elements of the use of stem cells in reproductive medicine, the book also contains a section on new developments in stem cell research. The book is essential reading for reproductive medicine clinicians, gynecologists and embryologists who want to keep abreast of practical developments in this rapidly developing field.

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Contents

  • 8 - Embryonic stem cells from blastomeres maintaining embryo viability
    pp 84-92
  • View abstract

    Summary

    This chapter reviews molecular mechanisms that control germline formation through a complex cascade of gene activation. In mammals, primordial germ cells (PGCs) are derived from the proximal epiblast during early embryogenesis. Interestingly, although both FRAGILIS and STELLA are differentially expressed in PGCs, neither appears to be essential for PGC specification. In general, migration of PGCs from primitive streak to genital ridges is believed to be governed by chemotactic cytokines, cell surface receptors, and cell adhesion factors. Until the colonization of the genital ridges, XX and XY PGCs are indistinguishable in terms of morphology and behavior. Mammalian male sex determination is initiated by sex-determining region Y (SRY) expression in XY genital ridges, which triggers Sertoli cell differentiation in supporting cell precursors. Germ-cell colonization of the gonads is followed by sex determination. Expression of sex-specific genes in somatic tissues initiates molecular events that lead to testis or ovary development.
  • 10 - Amniotic fluid and placental membranes: Uunexpected sources of highly multipotent cells
    pp 102-114
  • View abstract

    Summary

    To understand the most recent advances in germline differentiation from human pluripotent stem-cell lines in vitro, it is necessary to give a brief introduction of the basics of germline development in mammals. In mammals, germ cells arise from a pluripotent cell population called primordial germ cells (PGCs) that segregates from the somatic lineage during gastrulation in response to the Bone Morphogenetic Proteins 4 and 8 secreted by adjacent extra-embryonic endoderm. Once germ cells colonize gonadal ridges, expression of SRY, encoded on the short arm of the Y chromosome, drives their male sexual differentiation. Meiosis in mammals is a complicated process consisting in two consecutive cell divisions without DNA replication to generate haploid cells. This chapter reviews the main advances in germline differentiation from pluripotent stem cells, with special emphasis on the challenges to overcome in order to achieve the correct maturation of germ cells in vitro.
  • 11 - Adult stem cells in the human endometrium
    pp 115-132
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    Summary

    This chapter describes the existing knowledge regarding the ideal molecular profile of sperm cells, in order to define the model to be mimicked when stem cells are employed in order to create male gametes. Sperm production is defective in a significant proportion of males aiming at fatherhood. Interestingly, there are a significant proportion of infertile males presenting normal sperm counts, thus diagnosed as having idiopathic infertility. To date, there are a lot of studies concerning DNA analysis of human spermatozoa suggesting that the determination of DNA fragmentation levels can be a parameter of semen quality, directly implicated in male fertility. Sperm membrane lipid composition is of special interest, given their involvement in fertilization, capacitation, spermatozoa, and oocyte interaction. The future vision shows the possibility to create sperm cells from adult stem cells, with all the requirements to succeed fulfilled, thus guaranteeing a safe and successful use.
  • 13 - Bone-marrow stroma: A source of mesenchymal stem cells for cell therapy
    pp 140-151
  • View abstract

    Summary

    Spermatogonial stem cells (SSCs) enable continuous sperm production for almost the entire life of a male. Spermatogonial transplantation (SGT) was a revolutionary technique in the study of male germ-cell biology. Semen cryopreservation of young male cancer patients is becoming common in clinical practice. SSCs can be obtained from small fragmental testis tissues of pediatric cancer patients, taken by a biopsy procedure. The SSCs could be cryopreserved for later use, if patients survive the disease and grow to reproductive age. Most importantly, in vitro spermatogenesis circumvents the invasive procedure of cell transplantation, let alone the possible reintroduction of malignant cells to the patient when SSCs are cryopreserved. In vitro human spermatogenesis, just after the development of mouse in vitro spermatogenesis, might be a focus for research interest. It may not be easy to achieve. In particular, the duration of spermatogenesis is longer in humans (64 days) than in mice (35 days).
  • 14 - Dedifferentiation, transdifferentiation, and reprogramming
    pp 152-163
  • View abstract

    Summary

    This chapter provides an update on spermatogonial stem cells (SSCs), on their role in male fertility, and on (future) clinical applications using these fascinating cells. Spermatogenic proliferation and differentiation is accompanied by incomplete cell division, resulting in daughter cells, which remain interconnected by intercellular bridges. Spermatogonial stem cells can develop in three different ways: they can renew themselves, they can differentiate, or they can go into apoptosis. To safeguard the reproductive potential of young cancer patients, cryopreservation of testicular tissue containing SSCs is preferred above cryopreservation of SSC suspensions. The technique of spermatogonial stem-cell transplantation involves the introduction of a germ-cell suspension from a fertile donor testis into the seminiferous tubules of an infertile recipient mouse. Testicular tissue grating has been suggested as an alternative to spermatogonial stem-cell transplantation. Banking and transplantation of SSCs may become a promising method to preserve the fertility of prepubertal patients.
  • 15 - The metabolic framework of pluripotent stem cells and potential mechanisms of regulation
    pp 164-179
  • View abstract

    Summary

    This chapter reviews the sexually dimorphic nature of meiosis in mammalian species, since many aspects of recombination depend on whether the gamete is proceeding through spermatogenesis or oogenesis. Since meiotic recombination occurs at prophase during fetal development in mammalian females, few investigations of human recombination have focused on this stage. Linkage disequilibrium (LD) analysis provides a powerful tool for the generation of high resolution genetic maps. LD mapping does not require analysis of multiple generations in a family. Rather it is a simple assessment of haplotype blocks among different individuals. Fortunately, with improvements in immunostaining techniques and the increasing availability of antibodies capable of detecting meiosis-acting proteins, it has now become possible to analyze the processes of pairing, synapsis, and recombination in human fetal oocytes. Advances in mapping methodology have led to the generation of high-resolution male and female genetic maps.

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