Bisphenol F Disrupts Thyroid Hormone Signaling and Postembryonic Development in Xenopus laevis

Abstract

The safety of bisphenol A (BPA) alternatives has attracted much attention due to their wide use. In this study, we investigated the effects of bisphenol F (BPF), an alternative to BPA, on thyroid hormone (TH) signaling and postembryonic development in vertebrates using T3-induced and spontaneous Xenopus metamorphosis as models. We found that in the T3-induced metamorphosis assay, higher concentrations of BPF (100-10000 nM) antagonized T3-induced TH-response gene transcription and morphological changes including intestinal remodeling in a concentration-dependent manner, whereas 10 nM BPF exerted stimulatory effects on T3-induced integral metamorphosis when inhibited T3-induced TH-response gene transcription, demonstrating TH signaling disrupting effects of BPF. In the spontaneous metamorphosis assay, correspondingly, BPF inhibited development at metamorphic climax (with high endogenous TH levels), but promoted pre- and pro-metamorphic development (with low endogenous TH levels), displaying a developmental stage-dependent manner. Importantly, we observed agonistic actions of BPF on Notch signaling in intestines, showing that BPF disrupts vertebrate development possibly via multi pathways besides TH signaling. Thus, we infer the biphasic concentration-response relationship between BPF exposure and T3-induced metamorphosis could result from the interactions of TH signaling with other signaling pathways such as Notch signaling. Our study highlights the adverse influences of BPF on vertebrate development.

Bisphenol F has different effects on preadipocytes differentiation and weight gain in adult mice as compared with Bisphenol A and S

“…When screened for activity in a yeast activity assay BPF was shown to have antagonist effects on the androgen receptor as well as glucocorticoid receptor, and in both cases the potency of BPF was slightly higher than BPA (Roelofs et al 2015). Recent studies have shown that, similar to BPA, BPF has the potential to interfere with the thyroid hormone (TH) signaling pathway (Zhang et al 2018;Zhu et al 2018). A final point is that multiple bisphenols are being detected in human tissues and the manner in which these compounds interact is nearly completely unknown (Kolatorova et al 2018).…”

A Multiwell-Based Assay for Screening Thyroid Hormone Signaling Disruptors Using thibz Expression as a Sensitive Endpoint in Xenopus laevis

“…Following this, the first-strand cDNA was stored at −20 °C for gene expression analysis. Expression of TH-response genes was analyzed using SYBR Green I with the Real-time Polymerase Chain Reaction system (Light Cycler 480, Roche, Basel, Switzerland), with Ribosomal protein L8 ( rpl8 ) as a reference gene [ 43 , 44 , 45 ] and the expression of rpl8 was not affected by treatments ( Supplementary Materials, Figures S1 and S2 ). In 10 µL of PCR reaction system, 1 µL of cDNA template, 0.3 µL of forward primer, 0.3 µL of reverse primer, 3.4 µL of DNase/RNase-free water, and 5 µL of 2 × SuperReal PreMix Plus were mixed.…”

Composition and endocrine effects of water collected in the Kibale national park in Uganda

“…While the majority mainly differ in exposure period and sometimes in the model employed, many of the same endpoints were investigated to identify potential THADCs (i.e., hindlimb length, snout-to-vent length, developmental stage and thyroid histology; Supplementary Table). In tadpoles, as morphological changes of the head region and the brain are induced by THs, measurements such as mouth width, head area, brain width, brain length, or olfactory-organ-to-brain length may further characterize disruption of TH-induced metamorphosis (Yao et al, 2017;Zhu et al, 2018;Mengeling et al, 2016Mengeling et al, , 2017. Several morphological endpoints were examined in conjunction with the readout of transgenic X. laevis tadpoles harbouring a luciferase reporter driven by TH/BZIP TREs (Mengeling et al, 2016(Mengeling et al, , 2017.…”