Embryonic developmental toxicity in marine medaka (Oryzias melastigma) caused by combined 17α-ethinylestradiol and hypoxic exposure

Hypoxia is one of the most pressing global challenges affecting aquatic ecosystems and is primarily driven by global warming and eutrophication. 17α-ethinylestradiol (EE2), a representative endocrine-disrupting chemical, is widely used in hormone therapy and contraceptives. Both hypoxia and EE2 affect embryonic development by disrupting endocrine signaling and their interactions may induce effects significantly different from their individual impacts. However, the combined exposure of aquatic animals to EE2 under hypoxic conditions remains poorly understood. In this study, marine medaka (Oryzias melastigma) were exposed to combined stressors of EE2 and hypoxia to investigate their interactive effects on embryonic development compared to individual exposures. The key parameters assessed were heart rate, hatching time, hatching rate, and larval locomotion. Our findings indicate that combined exposure to EE2 and hypoxia resulted in an additive effect eye pigmentation development and an antagonistic effect on hatching time. These results highlight the diverse trends in the effects induced by the interaction of multiple stressors, suggesting that in-depth omics-based analyses are required to explore the underlying molecular mechanisms. (Figure presented.)