Prospects of the Reproductive Toxicology: With Special Reference to the Developmental Hazards Due to the Treatment at the Stages from Prefertilization to Implantation*

With the definition of teratogenicity was expanded in terms of developmental stages when the agent acts and types of developmental anomalies induced, the concept of reproductive toxicity or developmental toxicity has been established. These new terms are essentially the synonym; the former gives the prime emphasis on the parent generation while the latter on the longer phase of developmental stage of the offspring. It has been generally stated that the environmental agents which act before the onset of organogenesis will bring the embryo either death or normal growth. However, some affect the preimplantation embryos with resultant congenital anomalies. Moreover, it has been demonstrated that various developmental defects can be induced by a premating treatment to males, some of which may have been caused by mechanisms other than mutagenicity. On the other hand, oogenesis in females takes a very long time and it is often difficult to determine when these environmental agents act before or after pregnancy. Recent episodes of herbicides (Agent Orange) and vaginal spermicides were introduced as examples. Pharmaceutical drugs, chemicals given to humans intentionally at a relatively large amount in a limited duration, have been requested to be tested in laboratory animals on the possible developmental defects in offspring even when given prior to organogenesis. In Japan, at the test administered prior to and in the early stages of pregnancy (segment I study), it is recommended not only to examine fertility of the parent generation but also to observe the development of offspring as long as practically possible. In the symposium held at the 24th Annual Meeting of the Japanese Teratology Society, significance of developmental failures of the offspring induced by environmental factors given to the parents and during the preimplantation period was critically discussed.