Ovarian follicle bioassay reveals adverse effects of diazepam exposure upon follicle development and oocyte quality

A mouse ovarian follicle bioassay was used to study folliculogenesis and oocyte quality in vitro. Diazepam (DZ) was chosen as test compound to evaluate the system for its ability to detect possible effects of chemicals on reproduction. The bioassay is suitable to analyze the influence of DZ on each of the follicular components at any stage of development. A dose finding study revealed that follicle growth, differentiation and steroidogenesis were significantly disturbed by ≥5 μg/ml DZ. A transient exposure procedure was used to examine stage-specific sensitivities of oogenesis to DZ. The oocyte appeared to be most vulnerable during its growth process within the follicle. Resumption of meiosis was disturbed dose-dependently with reduced oocyte quality after chronic exposure to ≥2.5 μg/ml DZ. The bioassay is a highly efficient and informative tool to assess the hazards of chemical compounds for female fertility and to elucidate their mechanisms of action.