Life cycle of the mammalian germ cell: Implication for spontaneous mutation frequencies

A brief history of the developmental life cycle of the mammalian germ cell, from fertilization to gametogenesis in the mature gonad, is presented. The differences between gametogenesis in the mature gonad of males and females are also described with regard to properties that may affect their suscept ibilities to mutation. It is emphasized that any historical control backgro und rate of necessity will include mutations that occur in germinal tissue at all stages of development and differentiation, although it is not always possible to determine at what stage of germline development a spontaneous mutation has occurred. Studies of induced mutations suggest that the impact on the molecular level and the distribution of mutations among the F1 and F2 progeny may be partly determined by the stage and sex of germ cells in w hich spontaneous mutations occur. In summary, historical control rates shou ld only be considered the sum total of mutations that occur during the enti re life of the individual and cannot represent the control values of any in dividual germ cell stage. Nonetheless, it is certainly important and valid to use historical control data for calculating human risk, because the prim ary use of the estimation of mutant frequencies is to access the potential impact of agents in increasing the genetic load in the human population. (C ) 1999 Wiley-Liss, Inc.