Sex‐specific endocrine‐disrupting effects of three halogenated chemicals in Japanese medaka

• Published in: Journal of applied toxicology Vol. 39; no. 8; pp. 1215 - 1223
• Main Authors: Godfrey, Amy, Hooser, Blair, Abdelmoneim, Ahmed, Sepúlveda, Maria S.
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.08.2019
• Subjects: Bladder; Chemicals; Disruption; Embryos; Endocrine disruptors; estrogenic compounds; Exposure; Females; fish; flame retardants; Gender aspects; Gene expression; Genes; Halogenated compounds; Halogenation; Hypothyroidism; Males; Organic chemistry; Oryzias latipes; perfluorinated compounds (PFCs); Perfluorooctanoic acid; Sex; Sex differences; Swim bladder; Thyroid; thyroid disruption; Thyroid gland; Thyroid hormones; Toxicity; Triiodothyronine; Vitellogenin; Xenoestrogens; estrogenic compounds; thyroid disruption; flame retardants; swim bladder; perfluorinated compounds (PFCs); fish
• ISSN: 0260-437X; 1099-1263
• DOI: 10.1002/jat.3807

Several halogenated chemicals are found in an array of products that can cause endocrine disruption. Human studies have shown that endocrine responses are sex specific, with females more likely to develop hypothyroidism and males more likely to have reproductive impairment. The objective of this study was to assess sex differences on thyroid and estrogenic effects after exposure of Japanese medaka (Oryzias latipes, SK2MC) to halogenated compounds. This strain is an excellent model for these studies as sex can be determined non‐destructively a few hours postfertilization. Medaka embryos were exposed to sublethal concentrations of Tris(1,3‐dichloro‐2‐propyl) phosphate (TDCPP, 0.019 mg/L), perfluorooctanoic acid (PFOA, 4.7 mg/L) and its next generation alternative, perfluorobutyric acid (PFBA, 137 mg/L). Methimazole (inhibits thyroid hormone synthesis) and the thyroid hormone triiodothyronine served as reference controls. Fish were exposed throughout embryo development until 10 days postfertilization. Females displayed significantly larger swim bladders (which are under thyroid hormone control) after exposure to all chemicals with the exception of triiodothyronine, which caused the opposite effect. Females exposed to TDCPP and PFOA had increased expression of vitellogenin and exposure to PFOA upregulated expression of multiple thyroid‐related genes. Upregulation of estrogenic‐regulated genes after exposure to TDCPP, PFOA and methimazole was only observed in males. Overall, our results suggest that females and males show an estrogenic response when exposed to these halogenated chemicals and that females appear more susceptible to thyroid‐induced swim bladder dysfunction compared with males. These results further confirm the importance of considering sex effects when assessing the toxicity of endocrine‐disrupting compounds. Some halogenated chemicals have shown endocrine‐disrupting effects and sex‐specific responses. Our objective was to assess sex differences on thyroid and estrogenic effects after exposure of Japanese medaka (Oryzias latipes, strain SK2MC) to sublethal concentrations of halogenated compounds, Tris(1,3‐dichloro‐2‐propyl) phosphate, perfluorooctanoic acid and perfluorobutyric acid. Our results suggest that females and males show estrogenic responses when exposed to these halogenated chemicals but females appear more susceptible to thyroid‐induced swim bladder dysfunction.