Perfluorobutanesulfonate Interfering with the Intestinal Remodeling During <i>Lithobates catesbeiana</i> Metamorphosis via the Hypothalamic–Pituitary–Thyroid Axis

The intestinal remodeling during amphibian metamorphosis is essential for adapting to various ecological niches of aquatic and terrestrial habitats. However, whether and how the widespread contaminant, perfluorobutanesulfonate (PFBS) affects intestinal remodeling remains unknown. In this study, tadpoles (<i>Lithobates catesbeianus</i>) at the G26 stage were exposed to environmentally relevant concentrations of PFBS (0, 1, 3, and 10 μg/L) until the end of metamorphosis. PFBS exposure resulted in reduced thyroid follicular glia; down-regulation of gene transcripts related to thyroid hormone synthesis; decreased blood hormone (corticotropin-releasing hormone, thyroid-stimulating hormone, and 3,5,3'-triiodothyronine (T3)) and transthyretin concentrations; and up-regulation of gene transcripts related to thyroid hormone degrading enzymes. Moreover, exposure to PFBS induced apoptosis in single-layer columnar epithelial cells, suppressed the proliferation of intestinal stem cells, and hindered their differentiation into adult epithelial cells during intestinal remodeling. The responses of Notch and Wnt signaling pathways regulated by T3 were downregulated, and key gene transcripts (<i>msi</i>, <i>pcna</i>, and <i>lgr5</i>) involved in intestinal remodeling regulated by these two pathways were also downregulated. This is the first report on the effects of PFBS on amphibian metamorphosis. Overall, PFBS reduced thyroid hormone synthesis and transport by interfering with the hypothalamic-pituitary-thyroid axis and transthyretin expression, inhibited downstream Notch and Wnt signaling pathway responses, and ultimately led to incomplete intestinal remodeling to some extent.