LAUSR

Although medicines are less toxic than other toxicants, increased production and usage of pharmaceuticals have led to many concerns regarding their toxic effects on human and non-target organisms. Additionally, reproductive toxicity after long-term exposure is difficult to anticipate. Tamoxifen (TAM), a selective estrogen receptor modulator, has been widely used as an anticancer drug for mammalian breast and endometrial cancers. With increased TAM usage, it has frequently been reported that TAM is a potential endocrine disruptor capable of interfering with reproduction in non-target organisms. However, the mode of action of TAM in the endocrine system is unknown. In this study, we performed a 21-day chronic toxicity test using the crustacean Daphnia magna and investigated the transcriptional modulation of major genes related to the endocrine system, molting, development, and reproduction (i.e., Dm-vtg2, vmo1, cyp314, usp, and ecrb) after TAM exposure for 3, 6, 12, and 24 h. Our results showed a concentration-dependent decrease in the total number of offspring per individual, except for the concentration 25 μg/L; additionally, the expression of oogenesis-related genes was induced early but was later inhibited by TAM exposure. Additionally, molting-related genes were also downregulated in a time-dependent manner. Our findings suggested that TAM regulates reproduction by interfering with the molecular mechanisms involved in oogenesis and molting. This study supports the hypothesis that D. magna are a useful model to rapidly evaluate the reproductive effects of pharmaceuticals.