Dioctyl Sodium Sulfosuccinate as a Potential Endocrine Disruptor of Thyroid Hormone Activity in American bullfrog, Rana (Lithobates) catesbeiana, Tadpoles

Abstract

The thyroid hormones, thyroxine (T4) and triiodothyronine (T3), are required to regulate complex developmental processes in vertebrates and are highly sensitive to endocrine-disrupting compounds. Previous studies demonstrate that dioctyl sodium sulfosuccinate (DOSS), a common constituent of pharmaceuticals, cosmetics, and food products, disrupts canonical signaling of adipocyte differentiation by binding a nuclear hormone receptor in the same superfamily as thyroid hormone (TH) receptors. The present study was designed to determine whether DOSS is capable of disrupting TH signaling using the American bullfrog, Rana (Lithobates) catesbeiana—a cosmopolitan frog species that undergoes TH-dependent metamorphosis to transition from an aquatic tadpole to a terrestrial juvenile frog. Premetamorphic R. catesbeiana tadpoles were injected with 2 pmol/g body weight T3 or 10 pmol/g body weight T4 to induce precocious metamorphosis, then exposed for 48 h to environmentally or clinically relevant DOSS concentrations (0.5, 5, and 50 mg/L). Gene expression of three classical TH-responsive targets (thra, thrb, and thibz) was measured in tadpole liver and tail fin tissue through reverse transcription quantitative polymerase chain reaction (RT-qPCR). DOSS disrupted gene expression in liver and tail fin tissue at all three concentrations tested but the patterns of expression differed by tissue, gene transcript, and TH treatment status. To our knowledge, this is the first demonstration that DOSS can alter TH signaling. Further exploration into DOSS disruption of TH signaling is warranted, because exposure may affect other TH-dependent processes, such as salmon smoltification and perinatal human development.