The relationship between early deaths and implants in control and mutagen-treated CD-1 mice in dominant lethal assays

In dominant lethal assays it has been assumed that the number of early deaths per pregnancy is a function of the germ cells and is independent of maternal influence. It has also been assumed that there is a direct relationship between the number of early deaths and the total number of implants, which in turn has influenced dominant lethal studies. The present communication supports the view that at least this second assumption is erroneous. Data from dominant lethal assays using CD-1 mice in 2 laboratories have been compared and early deaths per implantation as a function of implantations were examined and the implications of the results generated have been considered. It was found in negative control data that a direct relationship between the numbers of early deaths and total implantations was true only at very low, possibly, very high total implantation numbers. Between 4 and 15 implant (based on over 7500 females) the average number of early deaths remained constant. After treatments the direct relationship seen at low implant numbers extended over a larger implant range, but above this range the average number of early deaths again tended to remain constant. It followed, therefore, that, when early deaths per implantation as a function of implantations was considered the average values were dependent on total implantation number over the whole range decreasing as implantations per pregnancy increased. The effect of the mutagens on the frequency of early deaths per implant was greater at low implant numbers. Approaches to statistical analysis of the data from these studies are discussed in the light of the findings and a model is proposed whereby these unexpected relationships between the number of early deaths and the numbers of implantations are explicable in terms of the properties of the germ cells in CD-1 mice, but they may also be affected by some aspect of the female's physiology.