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 potent ial health concern. This paper highlights data from mouse germ-cell mu tagenesis studies that have implications in the assessment of reproduc tive and developmental risks. The paper discusses the developmental an d reproductive consequences of induced chromosomal damage (structural rearrangements and numerical anomalies) and describes environmental ag ents that have been shown to produce such anomalies. Additionally, fac tors that influence the yield of genetic damage are addressed. Studies showing that the various germ-cell stages vary in their susceptibilit y 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 mal es and females in the susceptibility to mutagens is examined. Recent s tudies 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 envir onmental agents during the period from fertilization through the zygot e and the two-cell embryo. Recent work in the mouse has demonstrated t hat exposure during these early developmental stages leads to high fre quencies of external and visceral fetal malformations, as well as mid- to-late gestational death.