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

• Main Author: Kaufman, Matthew Howard
• Published: University of Edinburgh 1984
• Online Access: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.735316

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.