The effect of rubella and herpesvirus homonis on the pre- and post-implantation stages of pregnancy in laboratory animals.

The teratogenic effect of rubella virus in humans has now been well documented (Ingalls, Plotkin, Meyer & Parkman, 1967) and virus isolation studies have suggested that rubella virus causes embryopathy by actually infecting the cells of the developing foetus (Alford, Neva & Weller, 1964). However, a laboratory animal model is required for controlled studies of the teratogenic activity of rubella virus and for the assessment of possible preventative measures. Such an animal system would also be useful for screening attenuated rubella vaccine strains for teratogenic properties. Pregnant primates have been used in preliminary experiments with rubella virus (Parkman, Phillips & Meyer, 1965) but suffer from the disadvantages of size, expense and difficulty of mating. Both the hamster (Ferm & Kilham, 1965) and the rabbit (Gibson, Staples & Newberne, 1966) have proved useful animals for the investigation of teratogenic agents. We have described previously the adaptation of strains of rubella virus to small laboratory animals (Oxford & Schild, 1966; Oxford, 1967) and wish now to report studies of the infection of rabbits and hamsters with rubella virus in the early stages of pregnancy. It was considered necessary during the development of such an animal model of teratogenicity to control the possibility that any embryopathic effect could be caused indirectly by passage of toxic metabolites rather than by passage of infective virus (Coffey & Jessop, 1959). Therefore the pre-implantation rabbit blastocyst (Lutwak-Mann & Hay, 1962) was used in the present study to detect any toxic activity. The rabbit blastocyst at this stage has been shown to be very sensitive to the toxic action of a number of agents (Lutwak-Mann & Hay, 1962). In addition, it is unlikely that any infective virus particles could reach the blastocyst before implantation (Zimmermann, Gottschewski, Flamm & Kunz, 1963). In contrast, the post-implantation foetal stages of both the hamster and the 1 Author's address: University of Sheffield Virus Research Laboratory, Lodge Moor Hospital, Sheffield, 10, England. 2 Author's address: Institute of Child Health, Great Ormond Street, London, England.