Toxicology of the female reproductive tract in standard fertility study designs

抄録

Fertility is just one measure of reproductive function; parturition and lactation are other measures of female reproductive function. Standard fertility studies to evaluate toxicity to the female reproductive tract are designed to evaluate gamete maturation, mating, behavior, fertilization, reproductive function, pre-implantation development and implantation. Generally, female germ cell toxicity will be detected by endpoints measured in standard fertility study designs. If the studies incorporate oocyte quantification then the female germ cell as a target of toxicity can be ascertained. Most reproductive toxicants that have been shown to kill primordial or growing follicles are genotoxic, however, not all genotoxicants are ovarian follicle toxicants. Due to the complexity of normal female reproductive physiology, both in humans and standard rodent models, there are many different ways for xenobiotics to manifest reproductive toxicity. This myriad of potential mechanisms of toxicity is a primary reason why no defined hierarchy of sensitivity is applicable for the typical endpoint measured in standard fertility study designs. A weight-of-the-evidence approach incorporating the multiplicity of endpoints is the most prudent when determining a true impact on reproductive function. If a pattern of changes across endpoints in these study types are observed in a specific reproductive process where the mode of action is well understood and conserved across species, this should be considered a threat to human health unless data is available to the contrary.