Reproductive toxicity in marine medaka (Oryzias melastigma) due to embryonic exposure to PCB 28 or 4'-OH-PCB 65

Previous studies have shown that juvenile or adult exposure to polychlorinated biphenyls (PCBs) induces alterations in reproductive functions (e.g., reduced fertilization rate) and behavior (e.g., reduced nest maintenance) in fish. Embryonic exposures to other endocrine disrupting chemicals have been reported to induce long-term reproductive toxicity in fish. However, the effects of embryonic exposure to PCBs or their metabolites, OH-PCBs, on long-term reproductive function in fish are unknown. In the present study, we used the marine medaka fish (Oryzias melastigma) as a model to assess the reproductive endpoints in response to embryonic exposure to either PCB 28 or 4'-OH-PCB 65. Our results showed that the sex ratio of marine medaka was feminized by exposure to 4'-OH-PCB 65. Fecundity was decreased in the medaka treated with either PCB 28 or 4'-OH-PCB 65, whereas the medaka from embryonic exposure to 4'-OH-PCB 65 additionally exhibited reduced fertilization and a reduction in the hatching success rate of offspring, as well as decreased sperm motil-ity. Serum 11-KT concentrations were reduced in the PCB 28-treated medaka, and serum estradiol (E2)/testosterone (T) and E2/11-ketotestosterone (11-KT) ratios were decreased in the 4'-OH-PCB 65-treated medaka. To explain these ob-servations at the molecular level, transcriptomic analysis of the gonads was performed. Bioinformatic analysis using Gene Ontology and Ingenuity Pathway Analysis revealed that genes involved in various pathways potentially involved in repro-ductive functions (e.g., steroid metabolism and cholesterol homeostasis) were differentially expressed in the testes and ovaries of either PCB-or OH-PCB-treated medaka. Thus, the long-term reproductive toxicity in fish due to embryonic ex-posure to PCB or OH-PCB should be considered for environmental risk assessment.