Kaufman, Matthew Howard

2018-01-31T11:46:14Z

2018-01-31T11:46:14Z

1984

In this thesis, the results of a considerable number of investigations into the genetic, morphogenetic and teratogenic factors that influence early mammalian development are presented. In virtually all of the investigations in which experimental procedures have been carried out, mouse embryos have been studied as embryos from this species have the singular advantage that all stages of gestation are easily accessible, and following their isolation and explantation into tissue culture may be maintained for lengthy periods of time in vitro with minimal obvious detrimental effect on their growth or development potential.

In the majority of the studies presented here, the principally genetic factors that influence the development of the pre-implantation conceptus have been analysed. In many of these studies the development potential of (diploid) fertilized embryos has been compared with that of parthenogenetically activated embryos which have been induced to develop under controlled experimental conditions in vitro. By definition, such embryos develop from a female gamete in the absence of any contribution from a male gamete. By comparing the development of appropriate groups of embryos, it has been possible to investigate the effect of homozygosity versus heterozygosity, and ploidy as well as analysing the influence of aneuploidy on early mouse embryonic development. In addition, this experimental approach has enabled, albeit indirectly, the influence of the fertilizing spermatozoon to be studied. Haploid and diploid parthenogenetically activated embryos are also capable of surviving into the early post-implantation period, and when combined in a chimaeric association with fertilized embryos adult mice are obtained in which the parthenogenetically-derived cells are capable of contributing to all the tissues of the body including the germ cells.

Studies are also described in which pluripotential cells have been established initially from fertilized embryos but subsequently from both haploid and diploid parthenogenones. Both fertilized- and parthenogenetically-derived cells have also been used to investigate the genetic and morphogenetic factors that influence early mammalian development.

Because the events that occur in the early post-implantation period are generally less well understood than those occurring during the pre-implantation period, various descriptive studies have been carried out which have sought to investigate the normal morphological changes that occur in the embryo at and shortly after implantation. More particularly, the events associated with the organogenesis of the neural tube and heart have been studied as these are the first major organ systems to develop within the embryo. In addition to these accounts of the normal development of these systems, studies are described in which embryos were exposed, either in vivo or in vitro, to a wide range of potentially teratogenic stimuli. Using this approach, a variety of studies have been carried out which have enabled the morphogenetic and to a lesser extent the genetic factors that influence early post-implantation mammalian development to be investigated. These studies clearly demonstrate that most of the agents tested appear to influence the cellular cytoskeletal system and in consequence interfere with the normal cell shape changes that should occur during organogenesis. Some of these agents are also capable of interfering with chromosome segregation during the meiotic divisions associated with oocyte maturation.

1. Kaufman, M.H., & Whittingham, D.G. (1972). Viability of mouse oocytes ovulated within 14 hours of an injection of pregnant mare's serum gonadotrophin. J. Reprod. Fert., 28, 465-468. | 2. Kaufman, M.H. (1972). Non-random segregation during mammalian oogenesis. Nature, Lond., 238, 465-466. | 3. Kaufman, M.H. (1973). Parthenogenesis in the mouse. Nature, Lond., 242, 475-476. | 4. Kaufman, M.H. (1973). Timing of the first cleavage division of the mouse and the duration of its component stages: a study of living and fixed eggs. J. Cell Sci., 12, 799-808. | 5. Kaufman, M.H. (1973). Timing of the first cleavage division of haploid mouse eggs, and the duration of its component stages. J. Cell Sci., L3> 553-566. | 6. Suominen, J., Kaufman, M.H., & Setchell, B.P. (1973). Prevention of fertilization in vitro by an acrosin inhibitor from rete testis fluid of the ram. J. Reprod. Fert., 34, 385-388. | 7. Kaufman, M.H. (1973). Analysis of the first cleavage division to determine the sex-ratio and incidence of chromosome anomalies at conception in the mouse. J. Reprod. Fert., 35, 67-72. | 8. Kaufman, M.H. & Surani, M.A.H. (1974). The effect of osmolarity on mouse parthenogenesis. J. Embryol. exp. Morph., 31, 513- 526. | 9. Kaufman, M.H. & Gardner, R.L. (1974). Diploid and haploid mouse parthenogenetic development following in vitro activation and embryo transfer. J. Embryol. exp. Morph., 31, 635-642. | 10. Phillips, R.J.S. & Kaufman, M.H. (1974). Bare-patches, a new sex-linked gene in the mouse, associated with a high production of XO females. II Investigations into the nature and mechanisms of the XO production. Genet. Res., 24, 27-41. | 11. Kaufman, M.H., Huberman, E. & Sachs, L. (1975). Genetic control of haploid parthenogenetic development in mammalian embryos. Nature, Lond., 254, 694-695. | 12. Kaufman, M.H. (1975). Parthenogenetic activation of mouse oocytes following avertin anaesthesia. J. Embryol. exp. Morph., 33, 941-946. | 13. Kaufman, M.H. (1975). The experimental induction of partheno¬ genesis in the mouse. In: The Early Development of Mammals. Ed. M. Balls & A.E. Wild, Cambridge University Press, Cambridge, 25-44. | 14. Kaufman, M.H. & Sachs, L. (1975). The early development of haploid and aneuploid parthenogenetic embryos. J. Embryol. exp. Morph., 34, 645-655. | 15. Kaufman, M.H. & Sachs, L. (1976). Complete preimplantatlon development in culture of parthenogenetic mouse embryos. J. Embryol. exp. Morph., 35, 179-190. | 16. Kaufman, M.H. (1976). The incidence of chromosomally unbalanced gametes in T (14; 15)6 Ca heterozygote mice. Genet. Res., 27, 77-84. | 17. Kaufman, M.H. & Steele, C.E. (1976). Deleterious effect of an anaesthetic on cultured mammalian embryos. Nature, Lond., 260, 782-784. | 18. Kaufman, M.H. (1977). Effect of anaesthesia on the outcome of pregnancy in female mice. J. Reprod. Fert., 49, 167-168. | 19. Kaufman, M.H., Barton, S.C. & Surani, M.A.H. (1977). Normal postimplantation development of mouse parthenogenetic embryos to the forelimb bud stage. Nature, Lond., 265, 53-55. | 20. Kaufman, M.H. (1977). Effect of anaesthetic agents on eggs and embryos. In: Development in Mammals, Vol. 1, Ed. M.H. Johnson, Elsevier/North Holland Biomedical Press B.V. 137- 163. | 21. Surani, M.A.H. & Kaufman, M.H. (1977). Influence of extracellular 2+ 2+ Ca and Mg ions on the second meiotic division of mouse oocytes: relevance to obtaining haploid and diploid parthenogenetic embryos. Devi. Biol,, 59, 86-90. | 22. Surani, M.A.H., Barton, S.C. & Kaufman, M.H. (1977). Development to term of chimaeras between diploid parthenogenetic and fertilised embryos. Nature, Lond., 270, 601-603. | 23. Kaufman, M.H., Guc-Cubrilo, M. & Lyon, M.F. (1978). X chromosome inactivation in diploid parthenogenetic mouse embryos. Nature, Lond., 271, 547-549. | 24. Kaufman, M.H. (1978). Chromosome analysis of early postimplantation presumptive haploid parthenogenetic mouse embryos. J. Embryol. exp. Morph., 45, 85-91. | 25. Kaufman, M.H. (1978). The experimental production of mammalian parthenogenetic embryos. In: Methods in Mammalian Reproduction. Ed. J.C. Daniel, Jr., Freeman, San Francisco, 21-47. | 26. Kaufman, M.H. & O'Shea, K.S. (1978). Induction of monozygotic twinning in the mouse. Nature, Lond., 276, 707-708. | 27. O'Shea, K.S. & Kaufman, M.H. (1979). The teratogenic effect of acetaldehyde: implications for the study of the fetal alcohol syndrome. J. Anat., 128, 65-76. | 28. Kaufman, M.H. (1979). Mammalian parthenogenetic development. Bibliography (with review). Bibliography of Reproduction. 33, 261-264, 341-343. | 29. Readhead, C., Kaufman, M.H., Schuetz, A.W. & Abraham, G.E. (1979). Relationship between steroidogenesis and oocyte maturation in rat Graafian follicles cultured in vitro. In: Ovarian Follicular and Corpus Luteum Function. Ed. C.P. Channing, J.M. Marsh, W.A. Sadler. Adv. Exp. Med. Biol., 112, 293-300. | 30. O'Shea, K.S. & Kaufman, M.H. (1979). Influence of copper on the early post-implantation mouse embryo: an in vivo and in vitro study. Roux Archives, 186, 297-308. | 31. Kaufman, M.H. (1979). Cephalic neurulation and optic vesicle formation in the early mouse embryo. Am. J. Anat., 155, 425- 444. | 32.O'Shea, K.S. & Kaufman, M.H. (1980). Copper-induced microtubule degeneration and filamentous inclusions in the neuroepithelium of the mouse embryo. Acta Neuropathologica, 49, 237-240. | 33. Rastan, S., Kaufman, M.H., Handyside, A.H. & Lyon, M.F. (1980). X-chromosome inactivation in extra-embryonic membranes of diploid parthenogenetic mouse embryos demonstrated by differential staining. Nature, Lond., 288, 172-173. | 34. O'Shea, K.S. & Kaufman, M.H. (1980). Phospholipase C-induced neural tube defects in the mouse embryo. Experientia, 36, 1217-1219. | 35. O'Shea, K.S. & Kaufman, M.H. (1980). Neural tube closure defects following in vitro exposure of mouse embryos to xylocaine. J. exp. Zool., 214, 235-238. | 36. O'Shea, K.S. & Kaufman, M.H. (1981). Effect of acetaldehyde on the neuroepithelium of early mouse embryos. J. Anat., 132, 107-118. | 37. Kaufman, M.H. (1981). Parthenogenesis: a system facilitating understanding of factors that influence early mammalian development. In: Progress in Anatomy, Vol. 1. Ed. R.J. Harrison & R.L. Holmes. Cambridge University Press 1-34. | 38. Kaufman, M.H. (1981). The role of embryology in teratological research, with particular reference to the development of the neural tube and heart. J. Reprod. Fert., 62, 607-623. | 39. Evans, M.J. & Kaufman, M.H. (1981). Establishment in culture of pluripotential cells from mouse embryos. Nature, Lond., 292, 154-156. | 40. Kaufman, M.H. & Navaratnam, V. (1981). Early differentiation of the heart in mouse embryos. J. Anat., 133, 235-246. | 41. Kaufman, M.H. & Woollam, D.H.M. (1981). The passage to the foetus and liquor amnii of ethanol administered orally to the pregnant mouse. Br. J. exp. Path., 62, 357-361. | 42. Brailsford, J.A.D. & Kaufman, M.H. (1982). Indirect estimation of crown-rump lengths of incomplete conceptuses from analysis of spinal-cord dimensions. Devel. Med. Child Neurology, 24, 603- 614. | 43. Kaufman, M.H. (1982). The chromosome complement of singlepronuclear haploid mouse embryos following activation by ethanol treatment. J. Embryol. exp. Morph., 71, 139-154. | 44. Kaufman, M.H. (1982). Two examples of monoamniotic monozygotic twinning in diploid parthenogenetic mouse embryos. J. exp. Zool., 224, 277-282. | 45. Kaufman, M.H., Robertson, E.J., Handyside, A.H. & Evans, M.J. (1983). Establishment of pluripotential cell lines from haploid mouse embryos. J. Embryol. exp. Morph., 73, 249-261. | 46. Kaufman, M.H. (1983). Ethanol-induced chromosomal abnormalities at conception. Nature, Lond., 302, 258-260. | 47. Evans, M.J. & Kaufman, M.H. (1983). Pluripotential cells grown directly from normal mouse embryos. Cancer Surveys, 2, 185- 207. | 48. Robertson, E.J., Evans, M.J. & Kaufman, M.H. (1983). X-chromosome instability in pluripotential stem cell lines derived from parthenogenetic embryos. J. Embryol. exp. Morph., 74, 297- 309. | 49. Robertson, E.J., Kaufman, M.H., Bradley, A. & Evans, M.J. (1983). Isolation, properties, and karyotype analysis of pluri¬ potential (EK) cell lines from normal and parthenogenetic embryos. Cold Spring Harbor Conferences on Cell Proliferation, 10, Teratocarcinoma Stem Cells (Eds. L.M. | 50. Silver, G.R. Martin & S. Strickland), pp. 647-663. Kaufman, M.H. (1983). The origin, properties and fate of trophoblast in the mouse. In: Biology of Trophoblast. Ed. Y.W. Loke & A. Whyte. Elsevier/North-Holland Biomedical Press pp. 23-68. | 51. Kaufman, M.H. (1983). Early Mammalian Development: Parthenogenetlc Studies. Cambridge University Press. | 52. O'Shea, K.S. & Kaufman, M.H. (1983). Chromosome translocation (T(2;4)l Sn) - induced neural tube defects in the mouse embryo. J. Neurogenetics, 29-38. | 53. Evans, M.J., Robertson, E.J., Bradley, A. & Kaufman, M.H. (1983). The relationship between embryonal carcinoma cells and embryos. In: Current Problems in Germ Cell Differentiation (Eds. A. McLaren & C.C. Wylie). B.S.D.B. Symposium, No. 7, 139-155. | 54. Kaufman, M.H. (1983). Occlusion of the neural lumen in early mouse embryos analysed by light and electron microscopy. J. Embryol. exp. Morph., 78, 211-228. | 55. Kaufman, M.H., Evans, M.J., Robertson, E.J. & Bradley, A. (1984). Influence of injected pluripotential (EK) cells on haploid and diploid parthenogenetic development. J. Embryol. exp. Morph., 80, 75-86. | 56. Kaufman, M.H. & Bain, I.M. (1984). Influence of ethanol on chromosome segregation during the first and second meiotic divisions in the mouse egg. J. exp. Zool., (in press). | 57. Bradley, A., Evans, M., Kaufman, M.H. & Robertson, E. (1984). Formation of germ-line chimaeras from embryo-derived teratocarcinoma cell lines. Nature, Lond., (in press). | 58. Kaufman, M.H. & Bain, I.M. (1984). The development potential of ethanol-induced monosomic and trisomic conceptuses in the mouse. J. exp. Zool., (in press).

http://hdl.handle.net/1842/28325

The University of Edinburgh

Annexe Thesis Digitisation Project 2017 Block 16

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Investigations into the genetic, morphogenetic and teratogenic factors that influence early mammalian development

Thesis or Dissertation

DSc Doctor of Science