β-estradiol 17-valerate affects embryonic development and sexual differentiation in Japanese medaka (Oryzias latipes)

β-estradiol 17-valerate (EV) is a synthetic estrogen widely used in combination with other steroid Hormones in hormone replacement therapy drugs and is detected in natural waters. Although EV is known as an estrogenic chemical, there is still a lack of data on its developmental and reproductive toxicities in fish following exposure to EV during embryo-larval-, juvenile- and adult-life stages in Japanese medaka (Oryzias latipes). At the early life stage, the fertilized eggs of medaka were exposed to 1, 10, 100 and 1000 ng/L EV for 15 days, and hatched larval fish were continually exposed to the same concentration range for an additional 15 days. The results showed that exposure to 10 ng/L or above resulted in adverse effects on hatchability and time to hatching, and the number of hatched females was twice that of males at 10 ng/L or above. When the hatched fish were continually exposed to 1, 10 and 100 ng/L of EV for another 40 days, the hepatosomatic index (HSI) was increased in both males and females, and the gonadosomatic index (GSI) was decreased in females, and increased in males. Sex reversal was found in fish exposed to 1 ng/L and above. Quantitative real-time RT-PCR showed that mRNA levels of Estrogen Receptor α (ER-α) and vitellogenin-I (VTG-I) in the liver of females were significantly down-regulated, while those of vitellogenin-I (VTG-I) in the liver of males were significantly up-regulated at all concentrations. These findings suggest that EV is a reproductive toxicant and estrogenic chemical in both male and female fish.