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BHPF
Toxics · 2025 ·Vol. 13 ·期 2 ·100 · IF 4.1

Integrated Metabolomic and Transcriptomic Analysis Revealed the Mechanism of BHPF Exposure in Endometrium

Xin Tan,Nengyong Ouyang,Wenjun Wang,Junting Qiu

Fluorene-9-bisphenol (BHPF) has been increasingly used as a bisphenol A substitute in the synthesis of various products. Previous studies have suggested that BHPF can be released from plastic bottles into drinking water, and BHPF accumulation has been reported to cause various adverse effects in humans. Nevertheless, the impact of BHPF exposure on endometrial epithelial cells remains largely unexplored. Here, we investigated the effects of exposure to different concentrations of BHPF on endometrial cells and used integrated metabolomic and transcriptomic methods to elucidate the underlying molecular mechanisms. Our results revealed significant associations between specific metabolites and genes, indicating that low-concentration exposure to BHPF affects endometrial epithelial cells by targeting pathways related to primary immunodeficiency, in which the key genes are IL7R and PTPRC . High-concentration exposure to BHPF decreased cell viability by regulating the purine metabolism pathway, as well as dysregulating the expression of PGM1 , PDE3B , AK9, and ENTPD8 . Our study highlights that the health risk of BHPF exposure to endometrial epithelial cells is concentration-dependent and that integrated analysis of metabolomic and transcriptomic data not only revealed the biological effects of BHPF and its underlying mechanisms, but also provided key candidate target genes for further exploration.

CAS / MDL: 67-56-1
研究领域: 毒理学 · 分子生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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ENVIRONMENTAL SCIENCE & TECHNOLOGY · 2022 · IF 11.357

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

Xiaolin Fan,Jilong Guo,Xiaojing Jia,Xingtai Mao,Ying Zhou,Yue Wang,Xuan Guo,Jiashu Shen,Narma Huai,Kailun Zhang,Abida Abdusalam,Hongxia Hu,Hua Zhu,Chengxia Jia,Lan Cheng,Xiqing Li,Zhaobin Zhang

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. Toxico-transcriptome 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.

CAS / MDL: 10540-29-1
研究领域: 环境科学 · 毒理学 · 水生生态学 · 分子生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY · 2024 · IF 6.2

Fluorene-9-bisphenol impaired male fertility through disrupting the testicular function and local microenvironment

Danni Jiang,Yang Yang,Xiaojuan Han,Qianni Li,Pengfei Li,Yang Xu,Lan Chao

Past studies have observed that BHPF induces multi-organ toxicity, however, whether it induces damage to male reproductive system and the specific mechanism remains unclear. In the present study, male mice were given 0, 2, 10 or 50 mg/kg/day of BHPF by gavage for 35 days to observe its effect on reproductive organ and sperm quality. The results indicated that BHPF decreased sperm count and sperm motility in a dose-dependent manner. Besides, our results demonstrated that BHPF triggered the proliferation inhibition and cell death of germ cells in vivo and in vitro. Also, BHPF reduced the expression of function markers for germ cells, Sertoli cells, and Leydig cells, indicating its damage to function of testis cells. Simultaneously, testicular microenvironment was found to be altered by BHPF, as presented with declined testosterone level and decreased expression of local microenvironment regulators. Overall, our findings indicated the detrimental effects of BHPF on male reproductive function in mice, suggesting testicular function and local microenvironment disturbance as mechanism underlying testicular damage.

研究领域: 毒理学 · 生殖生物学 · 内分泌学
✓ 已验证 DOI 高影响因子
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Nature Communications · 2017 ·Vol. 8 ·期 1 ·1-13 · IF 12.124

Fluorene-9-bisphenol is anti-oestrogenic and may cause adverse pregnancy outcomes in mice

Zhang Zhaobin,Hu Ying,Guo Jilong,Yu Tong,Sun Libei,Xiao Xuan,Zhu Desheng,Nakanishi Tsuyoshi,Hiromori Youhei,Li Junyu,Fan Xiaolin,Wan Yi,Cheng Siyu,Li Jun,Guo Xuan,Hu Jianying

Bisphenol A (BPA) is used in the production of plastic but has oestrogenic activity. Therefore, BPA substitutes, such as fluorene-9-bisphenol (BHPF), have been introduced for the production of so-called ‘BPA-free’ plastics. Here we show that BHPF is released from commercial ‘BPA-free’ plastic bottles into drinking water and has anti-oestrogenic effects in mice. We demonstrate that BHPF has anti-oestrogenic activity in vitro and, in an uterotrophic assay in mice, induces low uterine weight, atrophic endometria and causes adverse pregnancy outcomes, even at doses lower than those of BPA for which no observed adverse effect have been reported. Female mice given water containing BHPF released from plastic bottles, have detectable levels of BHPF in serum, low uterine weights and show decreased expressions of oestrogen-responsive genes. We also detect BHPF in the plasma of 7/100 individuals, who regularly drink water from plastic bottles. Our data suggest that BPA substitutes should be tested for anti-oestrogenic activity and call for further study of the toxicological effects of BHPF on human health.

CAS / MDL: 10540-29-1
研究领域: 环境科学 · 毒理学 · 生殖生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Polymers · 2022 ·Vol. 14 ·期 18 ·3904 · IF 4.967

Synthesis and Characterization of a Self-Polycondensation Diazaphthalanone Monomer and Its Polymers from Polycondensation Reactions

Xin Liu,Xiaozhou Zhang,Jiawei Jiang,Hongge Jia,Xigao Jian,Jinyan Wang

Polyether ketone (PEK) plastics are linear thermoplastic polymers connected by at least one ether bond and at least one ketone bond on the aryl group. The reason for their excellent heat resistance, rigidity, and mechanical strength is that their main molecular chain contains plenty of aromatic rings and polar carbonyl groups, and their molecular chain presents a large rigidity and strong intermolecular force. In addition, the main chain contains a considerable number of ether bonds, resulting in a certain toughness. However, polyether ketone materials have the disadvantage of poor solubility because of their excellent rigidity. To improve the solubility of polyether ketone, the preparation method of a novel nitrogenous heterocyclic polyaromatic ether monomer, 2-(4-chlorophenyl)-2,3-dihydrophthalazine-1,4-dione (CDD), was proposed, and its activity of polymerization was studied. The average molecular weight of the poly(aryl ether ketone) containing a nitrogenous heterocyclic polyaromatic ether group obtained by self-polycondensation of CDD was 4.181 × 103kg/mol, and the yield was 90.5%. In order to further explore the activity of monomers, novel copolymerized poly(aryl ether ketone) (PBCD) containing a nitrogenous heterocyclic polyaromatic ether structure was prepared by ternary copolymerization with 4,4-difluorobenzophenone (DFBP) and bisphenol fluorene (BHPF) with high activity. The average molecular weight of PBCD was 72.793 × 103kg/mol, the molecular weight distribution was 2.344, and the yield was 88.1%. Fourier transform infrared spectroscopy (FT-IR) and1H NMR were used to confirm the structure of the obtained polymer. Through thermogravimetric analysis (TGA), the determined weight loss temperature of 5% under nitrogen was higher than 500 °C, indicating excellent thermal stability. Compared with the solubility of the binary copolymer containing fluorenyl poly(aryl ether ketone) (PBD), the polymer showed reasonable solubility in selective solvents such as chloroform andN,N-dimethylacetamide.Keywords:poly(aryl ether ketone);solubility;thermal properties

CAS / MDL: 3236-71-3 345-92-6
研究领域: 高分子科学 · 材料科学 · 化学工程
✓ 已验证 产品关联 DOI PubMed 高影响因子
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FOOD AND CHEMICAL TOXICOLOGY · 2023 · IF 4.3

Fluorene-9-bisphenol exposure damages the testis in mice through a novel mechanism of ferroptosis

Qiwen Feng,Yumeng Liu,Liping Zou,Mengying Lei,Changhong Zhu,Wei Xia

Fluorene-9-bisphenol (BHPF) is an emerging global endocrine-disrupting chemical found in numerous household products as a substitute of bisphenol A. Many studies have reported various toxicities associated with BHPF. However, the effect of BHPF on male reproduction, particularly on the structural integrity of the blood testis barrier (BTB) in mice, has not yet been extensively studied. Ferroptosis , a newly identified form of cell death, occurs in the testicular tissue following exposure to BPA, affecting male fertility. We investigated whether ferroptosis plays a role in BHPF-induced testicular damage. The findings indicated that BHPF exposure led decreases in serum testosterone (T) concentration and sperm concentration and motility in mice. Furthermore, BHPF disrupted the BTB by interfering with key BTB-related proteins, including Cx43, β-catenin, and ZO-1. Moreover, BHPF induced ferroptosis through the induction of lipid peroxidation, iron overload, oxidative stress , and mitochondrial dysfunction in the testicular tissue. Inhibition of ferroptosis using Fer-1 mitigated the BHPF-induced damage to the BTB and ferroptosis in TM4 cells. Overall, our findings indicated the detrimental effects of BHPF on male reproductive function in mice, suggesting ferroptosis as a mechanism underlying testicular damage.

研究领域: 毒理学 · 生殖生物学 · 内分泌学
✓ 已验证 DOI PubMed 高影响因子
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