Genetic anomalies in mammalian germ cells and their significance for human reproductive and developmental risk

The induction of heritable mutations in germ cells represents a potential health concern. This paper highlights data from mouse germ-cell mutagenesis studies that have implications in the assessment of reproductive and developmental risks. The paper discusses the developmental and reproductive consequences of induced chromosomal damage (structural rearrangements and numerical anomalies) and describes environmental agents that have been shown to produce such anomalies. Additionally, factors that influence the yield of genetic damage are addressed. Studies showing that the various germ-cell stages vary in their susceptibility to the induction of genetic damage are summarized. Of the chemicals evaluated in the male mouse, most appear to have their predominant or strongest effect on post-stem-cell stages. The differences between males and females in the susceptibility to mutagens is examined. Recent studies have shown that the female may be uniquely sensitive to certain mutagens. Finally, an important aspect of mutagenic risk is not only effects induced in developing germ cells but also the effects of environmental agents during the period from fertilization through the zygote and the two-cell embryo. Recent work in the mouse has demonstrated that exposure during these early developmental stages leads to high frequencies of external and visceral fetal malformations, as well as mid-to-late gestational death.