Structural bisphenol analogues differentially target steroidogenesis in murine MA-10 Leydig cells as well as the glucocorticoid receptor

Roelofs, Maarke J.E.; Berg, Martin van den; Bovee, Toine F.H.; Piersma, Aldert H.; Duursen, Majorie B.M. van

doi:10.1016/j.tox.2015.01.003

Cited by 106 publications

(60 citation statements)

References 73 publications

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“…Although the chemical structures of BPA and its analogues are similar, HCA demonstrated differential adverse effects of 4 bisphenols on multiple molecular and cellular events, suggesting that different mechanisms may promote cytotoxicity. Similar findings were reported in previous in vitro studies, in which BPAF and TBBPA showed higher endocrine modulating potentials in human MCF7 breast cancer cells and Leydig cells, respectively, as compared with BPA (Lei et al, 2016;Roelofs et al, 2015). BPS showed similar inhibitory effects with BPA on testosterone secretion in human fetal testes and induced more sensitive responses in mice testes (Eladak et al, 2015).…”

Section: Discussionsupporting

confidence: 90%

High-Content Analysis Provides Mechanistic Insights into the Testicular Toxicity of Bisphenol A and Selected Analogues in Mouse Spermatogonial Cells

Liang

Yin

et al. 2016

Toxicol. Sci.

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Bisphenol A (BPA), an endocrine-disrupting compound, was found to be a testicular toxicant in animal models. Bisphenol S (BPS), bisphenol AF (BPAF), and tetrabromobisphenol A (TBBPA) were recently introduced to the market as alternatives to BPA. However, toxicological data of these compounds in the male reproductive system are still limited so far. This study developed and validated an automated multi-parametric high-content analysis (HCA) using the C18-4 spermatogonial cell line as a model. We applied these validated HCA, including nuclear morphology, DNA content, cell cycle progression, DNA synthesis, cytoskeleton integrity, and DNA damage responses, to characterize and compare the testicular toxicities of BPA and 3 selected commercial available BPA analogues, BPS, BPAF, and TBBPA. HCA revealed BPAF and TBBPA exhibited higher spermatogonial toxicities as compared with BPA and BPS, including dose-and time-dependent alterations in nuclear morphology, cell cycle, DNA damage responses, and perturbation of the cytoskeleton. Our results demonstrated that this specific culture model together with HCA can be utilized for quantitative screening and discriminating of chemical-specific testicular toxicity in spermatogonial cells. It also provides a fast and cost-effective approach for the identification of environmental chemicals that could have detrimental effects on reproduction.

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Section: Discussionsupporting

confidence: 90%

High-Content Analysis Provides Mechanistic Insights into the Testicular Toxicity of Bisphenol A and Selected Analogues in Mouse Spermatogonial Cells

Liang

Yin

et al. 2016

Toxicol. Sci.

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“…While BPB suppressed testosterone production here (at 10 -7 M at both 24 and 48 h), its anti-androgenicity was close to that of BPA in the NCI-H295R cell line (Rosenmai et al, 2014). Further support for our findings comes from a study that used the mouse Leydig cell line, known as the MA-10 cell line (Roelofs et al, 2015).…”

Section: Inhibin Bsupporting

confidence: 75%

Parallel assessment of the effects of bisphenol A and several of its analogs on the adult human testis

et al. 2017

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WHAT IS KNOWN ALREADY:The few epidemiologic studies performed suggest that bisphenols have potential endocrine disruptive properties, but they did not identify clear and direct patterns of endocrine disruption. STUDY DESIGN, SIZE, DURATION:Adult human testis explants in culture were exposed to BPA and the analogs bisphenol F (BPF), bisphenol S (BPS), bisphenol E (BPE), bisphenol B (BPB), and bisphenol A diglycidyl ether (BADGE) at 10 -9 to 10 -5 M for 24 h or 48h.PARTICIPANTS/MATERIALS, SETTING, METHODS: Human adult testes were obtained from prostate cancer patients who had no hormone therapy, or from multiorgan donors. After ex vivo exposure to the investigated bisphenols, the measured outcomes were related to histopathology (gross morphology and germ cell viability determined by anti-caspase 3 immunohistochemistry), and the levels of testosterone, insulin-like fator 3 and inhibin B were measured using immunoassays. The levels of mRNA encoding key enzymes of bisphenol biotransformation were investigated by quantitative PCR: UGT2B15 UDP (glucuronosyltransferase two family, polypeptide B15), GUSB (glucuronidase beta), SULT1A1 and 3 (sulfotransferase family 1 A member 1 and 3) and STS (steroid sulfatase). MAIN RESULTS AND THE ROLE OF CHANCE: A significant dose-dependent inhibition wasfound between testosterone levels measured in the culture medium and concentrations of BPA The active concentrations of BPA and BPA-A used in the study were higher than those found in human biological fluids. WIDER IMPLICATIONS OF THE FINDINGS:Under our experimental conditions, direct exposure to BPA or BPA-A can result in endocrine disturbance in the adult human testis.

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“…BPA is an endocrine-disrupting chemical prevalent in the environment, and previous studies have focused on its effects on reproduction (32,33). Due to limited information concerning the toxic effect on the liver, the present study focused on evaluating the toxic effect of BPA and investigating the potential alleviation of BPA-induced injuries using a natural agent.…”

Section: Discussionmentioning

confidence: 99%

Protective effects of silymarin against bisphenol A-induced hepatotoxicity in mouse liver

Zăuleţ

Kevorkian

Dinescu

et al. 2017

Experimental and Therapeutic Medicine

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Bisphenol A (BPA) is an endocrine-disrupting chemical released into the environment, with severe consequences for human health, including metabolic syndrome and associated pathological conditions. Due to limited information on BPA-induced hepatotoxicity, the present study focused on investigating the association between BPA-induced toxicity and inflammatory markers in the liver, and how these injuries may be alleviated using the natural agent silymarin, a flavonoid with antioxidant properties obtained from Silybum marianum. Administration of BPA to male CD-1 mice for 10 days caused a significant increase in the number of cells immunopositive for interleukin 6 and tumor necrosis factor-α, pro-inflammatory cytokines that mediate the hepatic inflammatory response. Treatment with 200 mg/kg of silymarin concurrently with BPA for 10 days resulted in a diminished level of pro-inflammatory cytokines and in significantly reduced ultrastructural injuries. Additionally, silymarin was able to restore the significantly decreased glycogen deposits observed following BPA exposure to normal levels, thus favoring hepatic glycogenesis. This study represents the first report of silymarin ability to reduce hepatic lesions and to counteract inflammation caused by BPA in mice. A dose of 200 mg/kg silymarin was sufficient to induce a protective effect against structural and ultrastructural injuries induced by BPA and to lower the levels of pro-inflammatory cytokines observed in murine liver tissue following exposure to BPA.

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Structural bisphenol analogues differentially target steroidogenesis in murine MA-10 Leydig cells as well as the glucocorticoid receptor

Cited by 106 publications

References 73 publications

High-Content Analysis Provides Mechanistic Insights into the Testicular Toxicity of Bisphenol A and Selected Analogues in Mouse Spermatogonial Cells

High-Content Analysis Provides Mechanistic Insights into the Testicular Toxicity of Bisphenol A and Selected Analogues in Mouse Spermatogonial Cells

Parallel assessment of the effects of bisphenol A and several of its analogs on the adult human testis

Protective effects of silymarin against bisphenol A-induced hepatotoxicity in mouse liver

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