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
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
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.
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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-
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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,
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genesis in the mouse. In: The Early Development of Mammals.
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haploid and aneuploid parthenogenetic embryos. J. Embryol.
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| 15. Kaufman, M.H. & Sachs, L. (1976). Complete preimplantatlon
development in culture of parthenogenetic mouse embryos. J.
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| 16. Kaufman, M.H. (1976). The incidence of chromosomally unbalanced
gametes in T (14; 15)6 Ca heterozygote mice. Genet. Res., 27,
| 17. Kaufman, M.H. & Steele, C.E. (1976). Deleterious effect of an
anaesthetic on cultured mammalian embryos. Nature, Lond.,
| 18. Kaufman, M.H. (1977). Effect of anaesthesia on the outcome of
pregnancy in female mice. J. Reprod. Fert., 49, 167-168.
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postimplantation development of mouse parthenogenetic embryos
to the forelimb bud stage. Nature, Lond., 265, 53-55.
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| 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
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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
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Relationship between steroidogenesis and oocyte maturation in
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| 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-
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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.
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neural tube defects in the mouse embryo. Experientia, 36,
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following in vitro exposure of mouse embryos to xylocaine. J.
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pluripotential cells from mouse embryos. Nature, Lond., 292,
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the heart in mouse embryos. J. Anat., 133, 235-246.
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and liquor amnii of ethanol administered orally to the
pregnant mouse. Br. J. exp. Path., 62, 357-361.
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crown-rump lengths of incomplete conceptuses from analysis of
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haploid mouse embryos. J. Embryol. exp. Morph., 73, 249-261.
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at conception. Nature, Lond., 302, 258-260.
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instability in pluripotential stem cell lines derived from
parthenogenetic embryos. J. Embryol. exp. Morph., 74, 297-
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Isolation, properties, and karyotype analysis of pluri¬
potential (EK) cell lines from normal and parthenogenetic
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(T(2;4)l Sn) - induced neural tube defects in the mouse
embryo. J. Neurogenetics, 29-38.
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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,
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mouse embryos analysed by light and electron microscopy. J.
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| 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).