Abstract

The co-occurrence of hypoxia and xenobiotics is extremely common in natural environments, highlighting the necessity to elicit their interaction on aquatic toxicities. In the present study, marine medaka embryos were exposed to various concentrations (nominal 0, 1, 3.3 and 10 mg/L) of perfluorobutane sulfonate (PFBS), an environmental pollutant of emerging concern, under either normoxia (6.9 mg/L) or hypoxia (1.7 mg/L) condition. After acute exposure till 15 days post-fertilization, single or combined toxicities of PFBS and hypoxia on embryonic development (e.g., mortality, hatching and heartbeat) and endocrine systems were investigated. Sex and thyroid hormones were measured by enzyme-linked immunosorbent assay. Transcriptional changes of endocrine genes were determined by quantitative real-time PCR assays. Co-exposure to 10 mg/L PFBS and hypoxia caused a further reduction in survival rate and heart beat compared to single exposure. PFBS induced a precocious hatching, while no larvae hatched under hypoxia condition. By disturbing the balance of sex hormones, either PFBS or hypoxia single exposure produced an anti-estrogenic activity in medaka larvae. However, PFBS and hypoxia combinations reversed to estrogenic activity in co-exposed larvae. Variation in disrupting pattern may be attributed to the interactive effects on steroidogenic pathway involving diverse cytochrome P450 enzymes. Regarding thyroid system, PFBS exposure caused detriments of multiple processes along thyroidal axis (e.g., feedback regulation, synthesis and transport of thyroid hormones, receptor-mediated signaling and thyroid gland development), while hypoxia potently impaired the development and function of thyroid gland. Combinations of PFBS and hypoxia interacted to dysregulate the function of thyroid endocrine system. In summary, the present study revealed the dynamic interaction of PFBS pollutant and hypoxia on aquatic developmental toxicities and endocrine disruption. Considering the freque