Bisphenol A Deranges the Endocannabinoid System of Primary Sertoli Cells with an Impact on Inhibin B Production
Bisphenol A (BPA) is an endocrine disruptor that negatively affects spermatogenesis, a process where Sertoli cells play a central role. Thus, in the present study we sought to ascertain whether BPA could modulate the endocannabinoid (eCB) system in exposed mouse primary Sertoli cells. Under our expe...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-11-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/23/8986 |
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| author | Gianna Rossi Beatrice Dufrusine Anna Rita Lizzi Carla Luzi Alessandra Piccoli Filomena Fezza Roberto Iorio Gabriele D’Andrea Enrico Dainese Sandra Cecconi Mauro Maccarrone |
| author_facet | Gianna Rossi Beatrice Dufrusine Anna Rita Lizzi Carla Luzi Alessandra Piccoli Filomena Fezza Roberto Iorio Gabriele D’Andrea Enrico Dainese Sandra Cecconi Mauro Maccarrone |
| author_sort | Gianna Rossi |
| collection | DOAJ |
| description | Bisphenol A (BPA) is an endocrine disruptor that negatively affects spermatogenesis, a process where Sertoli cells play a central role. Thus, in the present study we sought to ascertain whether BPA could modulate the endocannabinoid (eCB) system in exposed mouse primary Sertoli cells. Under our experimental conditions, BPA turned out to be cytotoxic to Sertoli cells with an half-maximal inhibitory concentration (IC<sub>50</sub>) of ~6.0 µM. Exposure to a non-cytotoxic dose of BPA (i.e., 0.5 μM for 48 h) increased the expression levels of specific components of the eCB system, namely: type-1 cannabinoid (CB<sub>1</sub>) receptor and diacylglycerol lipase-α (DAGL-α), at mRNA level, type-2 cannabinoid (CB<sub>2</sub>) receptor, transient receptor potential vanilloid 1 (TRPV1) receptors, and DAGL-β, at protein level. Interestingly, BPA also increased the production of inhibin B, but not that of transferrin, and blockade of either CB<sub>2</sub> receptor or TRPV1 receptor further enhanced the BPA effect. Altogether, our study provides unprecedented evidence that BPA deranges the eCB system of Sertoli cells towards CB<sub>2</sub>- and TRPV1-dependent signal transduction, both receptors being engaged in modulating BPA effects on inhibin B production. These findings add CB<sub>2</sub> and TRPV1 receptors, and hence the eCB signaling, to the other molecular targets of BPA already known in mammalian cells. |
| first_indexed | 2024-03-10T14:32:49Z |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T14:32:49Z |
| publishDate | 2020-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-2f03e38b0f3c49769f2ccca2e408f6b32023-11-20T22:27:30ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-11-012123898610.3390/ijms21238986Bisphenol A Deranges the Endocannabinoid System of Primary Sertoli Cells with an Impact on Inhibin B ProductionGianna Rossi0Beatrice Dufrusine1Anna Rita Lizzi2Carla Luzi3Alessandra Piccoli4Filomena Fezza5Roberto Iorio6Gabriele D’Andrea7Enrico Dainese8Sandra Cecconi9Mauro Maccarrone10Department of Life, Health and Environmental Sciences, University of L’Aquila, 67100 L’Aquila, ItalyFaculty of Biosciences, and Technology for Food Agriculture and Environment, University of Teramo, 64100 Teramo, ItalyDepartment of Applied Clinical and Biotechnological Sciences, University of L’Aquila, 67100 L’Aquila, ItalyDepartment of Applied Clinical and Biotechnological Sciences, University of L’Aquila, 67100 L’Aquila, ItalyDepartment of Medicine, Campus Bio-Medico University of Rome, 00128 Rome, ItalyDepartment of Experimental Medicine and Surgery, Tor Vergata University of Rome, 00133 Rome, ItalyDepartment of Applied Clinical and Biotechnological Sciences, University of L’Aquila, 67100 L’Aquila, ItalyDepartment of Applied Clinical and Biotechnological Sciences, University of L’Aquila, 67100 L’Aquila, ItalyFaculty of Biosciences, and Technology for Food Agriculture and Environment, University of Teramo, 64100 Teramo, ItalyDepartment of Life, Health and Environmental Sciences, University of L’Aquila, 67100 L’Aquila, ItalyDepartment of Applied Clinical and Biotechnological Sciences, University of L’Aquila, 67100 L’Aquila, ItalyBisphenol A (BPA) is an endocrine disruptor that negatively affects spermatogenesis, a process where Sertoli cells play a central role. Thus, in the present study we sought to ascertain whether BPA could modulate the endocannabinoid (eCB) system in exposed mouse primary Sertoli cells. Under our experimental conditions, BPA turned out to be cytotoxic to Sertoli cells with an half-maximal inhibitory concentration (IC<sub>50</sub>) of ~6.0 µM. Exposure to a non-cytotoxic dose of BPA (i.e., 0.5 μM for 48 h) increased the expression levels of specific components of the eCB system, namely: type-1 cannabinoid (CB<sub>1</sub>) receptor and diacylglycerol lipase-α (DAGL-α), at mRNA level, type-2 cannabinoid (CB<sub>2</sub>) receptor, transient receptor potential vanilloid 1 (TRPV1) receptors, and DAGL-β, at protein level. Interestingly, BPA also increased the production of inhibin B, but not that of transferrin, and blockade of either CB<sub>2</sub> receptor or TRPV1 receptor further enhanced the BPA effect. Altogether, our study provides unprecedented evidence that BPA deranges the eCB system of Sertoli cells towards CB<sub>2</sub>- and TRPV1-dependent signal transduction, both receptors being engaged in modulating BPA effects on inhibin B production. These findings add CB<sub>2</sub> and TRPV1 receptors, and hence the eCB signaling, to the other molecular targets of BPA already known in mammalian cells.https://www.mdpi.com/1422-0067/21/23/8986endocrine disruptorinhibin Bmale reproductionreceptor signallingspermatogenesis |
| spellingShingle | Gianna Rossi Beatrice Dufrusine Anna Rita Lizzi Carla Luzi Alessandra Piccoli Filomena Fezza Roberto Iorio Gabriele D’Andrea Enrico Dainese Sandra Cecconi Mauro Maccarrone Bisphenol A Deranges the Endocannabinoid System of Primary Sertoli Cells with an Impact on Inhibin B Production International Journal of Molecular Sciences endocrine disruptor inhibin B male reproduction receptor signalling spermatogenesis |
| title | Bisphenol A Deranges the Endocannabinoid System of Primary Sertoli Cells with an Impact on Inhibin B Production |
| title_full | Bisphenol A Deranges the Endocannabinoid System of Primary Sertoli Cells with an Impact on Inhibin B Production |
| title_fullStr | Bisphenol A Deranges the Endocannabinoid System of Primary Sertoli Cells with an Impact on Inhibin B Production |
| title_full_unstemmed | Bisphenol A Deranges the Endocannabinoid System of Primary Sertoli Cells with an Impact on Inhibin B Production |
| title_short | Bisphenol A Deranges the Endocannabinoid System of Primary Sertoli Cells with an Impact on Inhibin B Production |
| title_sort | bisphenol a deranges the endocannabinoid system of primary sertoli cells with an impact on inhibin b production |
| topic | endocrine disruptor inhibin B male reproduction receptor signalling spermatogenesis |
| url | https://www.mdpi.com/1422-0067/21/23/8986 |
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