Chemical Impairment of Reproductive Functions.

Three areas of reproductive toxicology have been investigated in this thesis: the development of in vitro reproductive systems, the importance of male-mediated adverse effects on reproduction, and the action of reactive oxygen species and antioxidants in reproductive systems. In vitro reproductive techniques allow the separate observation of the functions of individual cell and tissue types and also give control over chemical treatment and measurement of toxicity. All those techniques used gave insight into some of the toxicological hazards for reproductive functions and also have value in initial assessments of toxicity. Separation of the maternal and embryonic components in embryotoxicity and protection was achieved through the use of post-implantation rat embryo cultures. The actions of a number of chemicals known to be toxic to the Sertoli cell were examined in an in vitro system, incorporating hepatocytes in a dual-compartment culture assembly to give the system metabolizing potential. The model was used to show that various chemicals required metabolism before toxicity to Sertoli cells became apparent. The effects of ethanol on the in vitro fertilizing capacity of mouse sperm were investigated following exposure to different dose regimens. None of those used showed an adverse effect of ethanol on fertilizing ability, implicating another aspect of the reproductive process. Infertility or testicular damage may result if the male reproductive system is disrupted by xenobiotics. It is being recognized increasingly that the offspring may be affected by chemical exposure of the male, as well as the female, to certain chemicals. The frequency of tumours, malformations and karyotype anomalies in the adult offspring has been investigated in rats after paternal exposure to cyclophosphamide. A small positive effect was observed, which could have implications for the exposure of human males to chemicals. Many chemicals known to have adverse effects on reproduction have the capacity to produce reactive oxygen species. The use of the xanthine/ xanthine oxidase radical-generating system in vitro has shown that reactive oxygen species may have a role in mediating reproductive toxicity. Cultured post-implantation embryos and cultured Sertoli cells were both adversely affected by this radical-generating system and protection was afforded by L-ascorbic acid (in embryos and Sertoli cells) and by DL-ɑ-tocopherol (in embryos only)