Reproductive Toxicity and Teratogenicity of Fluorene-9-bisphenol on Chinese Medaka (Oryzias sinensis): A Study from Laboratory to Field

Abstract

Fluorene-9-bisphenol (BHPF), a bisphenol A (BPA) substitute, has been increasingly used as a material in syntheses of polymers that are widely used in road markings, artificial tracks, coating floors, building paints, etc., increasing the likelihood of BHPF contamination in the aquatic environment due to its release from the products. However, to date, it is unknown whether it may have actual impacts on fish in real environments. In this study, a 105-day exposure experiment of BHPF at various concentrations (0.01, 0.1, 1, and 10 μg/ L) on Chinese medaka (Oryzias sinensis) was performed under laboratory conditions and found decreased fecundity, such as lower egg qualities and quantities, retarded oogenesis, and atretic follicles in the fish and deformed eyes and bodies in its F1 generation. Toxicotranscriptome analyses showed that estrogen-responsive genes were significantly suppressed by BHPF, indicating that antagonist properties of BHPF on estrogen receptors might be causes for the decreased fecundity. Field investigations (Beijing) demonstrated that BHPF was detectable in 60% surface waters, with a mean concentration of 10.49 ± 6.33 ng/L, by gas chromatography−mass spectrometry, and similar effects in wild Chinese medaka were also observed, some of which the parameters were found to be obviously correlated with the BHPF levels in corresponding waters.

Fluorene-9-bisphenol affects the terminal differentiation of mouse embryonic bodies

“…Intriguingly, our data revealed an upregulation of the Pou4F2 gene, a known marker for retinal ganglion cells, suggesting potential implications for visual development ( Badea and Nathans, 2004 ). This observation is consistent with recent findings in which eye malformation was reported in Chinese Medeka, a teleost fish, following exposure to BHPF at different concentrations for 105 days ( Fan et al, 2023 ). The upregulation of Pou4F2 and the associated eye malformation highlight the need for further studies to explore the impact of BHPF on visual development.…”

“…However, the potential toxicological impact of BHPF is still not fully understood. Moreover, BHPF has been found in household dust, further elevating concerns about widespread exposure ( Fan et al, 2023 ). Due to the growing public concern and regulatory pressure over BPA safety, some BPA alternatives have been introduced, such as BHPF.…”

YTHDF2-mediated regulations bifurcate BHPF-induced programmed cell deaths

“…Although this cannot be considered conclusive, it is interesting because fetus of pregnant participants with the highest levels of BHPF may develop VSD, suggesting that BHPF poses a potential threat to human fetal heart development. As humans and animals are exposed to environments polluted by BHPF [ 38 ], these findings should be made known to reduce environmental BHPF pollution and to promote further investigations on BHPF-mediated effects, including large-scale population studies. Furthermore, owing to the widespread application of BHPF-containing plastics, BHPF-releasing sources might already be inside human and animal bodies.…”

“…STING1) are also available, suggesting multiple potential therapeutic strategies targeting BHPF-induced adverse effects [ 43–45 ]. In addition to the frequent presence in serum of pregnant people, a recent report showed that BHPF is detectable in 60% of surface waters in Beijing, China [ 38 ], further highlighting the urgency for unveiling BHPF-mediated cardiovascular defects as well as potential therapeutic countermeasures. Our preclinical trial shows that sapropterin dihydrochloride can rescue heart failure in cardiomyocyte-specific Ythdf2 conditional knockout mice ( Supplementary Fig.…”

Transcriptome Analysis of the Developmental Effects of Bisphenol F Exposure in Chinese Medaka (Oryzias sinensis)

“…Chinese medaka has multiple advantages similar to the Japanese medaka, such as small body size, short generation time, genetic sexual determination, and well-annotated genomic information [ 38 ]. Furthermore, it is distributed in most parts of East Asia, and is convenient and suitable for both laboratory and field investigations [ 39 ]. The present study aims to examine the acute toxicity, developmental defects, and transcriptional alterations induced by BPF exposures in Chinese medaka embryos and provide information for understanding the health effects and ecological risk evaluation of BPF.…”