Reproduction and endocrine related effects of life-cycle exposure to 2-ethylhexyl 4-methoxycinnamate (EHMC), a sunscreen agent, in Japanese medaka (Oryzias latipes)

Abstract

2-Ethylhexyl 4-methoxycinnamate (EHMC) is one of the most frequently used UV-filters in personal care products (PCPs). Due to its widespread use, EHMC has been detected in aquatic biota as well as in surface waters. Despite its presence in aquatic environment, limited information on its toxicity in aquatic biota is available, especially in fish. In the present study, reproductive toxicity of EHMC and its underlying mechanisms were evaluated using Japanese medaka (Oryzias latipes), especially focusing on sex and thyroid hormone disruption. To fully understand the toxicity, a life-cycle test was conducted. Eggs within were exposed to 0, 0.05, 0.158, 0.5, 1.58, or 5 mg/L of EHMC. At juvenile stages of F0 generation, transcription of genes related to sex and thyroid hormone disruption was quantified. At adult stages, the fish were mated and the eggs were counted every day. At 5 months post-hatch (mph), genes related to sex and thyroid hormone disruption were analyzed in the liver and gonad of the F0 fish. Spawned eggs (F1 fish) were collected and used for early-life stage (ELS) toxicity test. In adult stages, plasma 17β-estradiol (E2) levels were not altered in both adult male and female. Decreasing patterns of transcript levels for steroidogenesis-related genes in ovary were observed. At juvenile stages of F1 generation, thyroid hormones and transcription of genes related to sex and thyroid hormone disruption was quantified. Significant decreased reproductive performances were observed observed in all treatment groups at as low as 0.05 mg/L, i.e., environmentally relevant concentration. Significant down-regulations of dio2 transcripts were observed at juvenile stages (31 day post-hatch (dph)) in both F0 and F1 generations. Whole-body triiodothyronine (T3) concentrations were significantly decreased and decreasing patterns of whole-body thyroxine (T4) concentrations, not between-group differences, were observed at juvenile stages of F1 generation. Our observations indicate that long-term exposure to EHMC can disrupt overall reproductive health outcomes and thyroid homeostasis during juvenile stages.