In the last decades, nanotechnology-based tools have attracted attention in the scientific community, due to their potential applications in different areas from medicine to engineering, but several toxicological effects mediated by these advanced materials have been shown on the environment and human health. At present, the effects of engineered nanomaterials on gametogenesis have not yet been well understood. In the present study, we addressed this issue using the yeast Saccharomyces cerevisiae as a model eukaryote to evaluate the effects of cadmium sulfide quantum dots (CdS QDs) on sporulation, a process equivalent to gametogenesis in higher organisms. We have observed that CdS QDs cause a strong inhibition of spore development with the formation of aberrant, multinucleated cells. In line with these observations, treatment with CdS QDs down-regulates genes encoding crucial regulators of sporulation process, in particular, the transcription factor Ndt80 that coordinates different genes involved in progression through the meiosis and spore morphogenesis. Down-regulation of NDT80 mediated by CdS QDs causes a block of the meiotic cell cycle and a return to mitosis, leading to the formation of aberrant, multinucleated cells. These results indicate that CdS QDs inhibit gametogenesis in an irreversible manner, with adverse effects on cell-cycle progression.