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Article

Bisphenol A Deranges the Endocannabinoid System of Primary Sertoli Cells with an Impact on Inhibin B Production

by
Gianna Rossi
1,†,
Beatrice Dufrusine
2,†,
Anna Rita Lizzi
3,†,
Carla Luzi
3,
Alessandra Piccoli
4,
Filomena Fezza
5,
Roberto Iorio
3,
Gabriele D’Andrea
3,
Enrico Dainese
2,‡,
Sandra Cecconi
1,‡ and
Mauro Maccarrone
3,6,*,‡
1
Department of Life, Health and Environmental Sciences, University of L’Aquila, 67100 L’Aquila, Italy
2
Faculty of Biosciences, and Technology for Food Agriculture and Environment, University of Teramo, 64100 Teramo, Italy
3
Department of Applied Clinical and Biotechnological Sciences, University of L’Aquila, 67100 L’Aquila, Italy
4
Department of Medicine, Campus Bio-Medico University of Rome, 00128 Rome, Italy
5
Department of Experimental Medicine and Surgery, Tor Vergata University of Rome, 00133 Rome, Italy
6
European Center for Brain Research, Santa Lucia Foundation IRCCS, 00142 Rome, Italy
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
‡
Equally senior authors.
Int. J. Mol. Sci. 2020, 21(23), 8986; https://doi.org/10.3390/ijms21238986
Submission received: 24 October 2020 / Accepted: 23 November 2020 / Published: 26 November 2020
(This article belongs to the Special Issue Central and Local Modulators of Reproduction and Fertility: An Update)
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Abstract

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 (IC50) 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 (CB1) receptor and diacylglycerol lipase-α (DAGL-α), at mRNA level, type-2 cannabinoid (CB2) 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 CB2 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 CB2- and TRPV1-dependent signal transduction, both receptors being engaged in modulating BPA effects on inhibin B production. These findings add CB2 and TRPV1 receptors, and hence the eCB signaling, to the other molecular targets of BPA already known in mammalian cells.
Keywords: endocrine disruptor; inhibin B; male reproduction; receptor signalling; spermatogenesis endocrine disruptor; inhibin B; male reproduction; receptor signalling; spermatogenesis

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MDPI and ACS Style

Rossi, G.; Dufrusine, B.; Lizzi, A.R.; Luzi, C.; Piccoli, A.; Fezza, F.; Iorio, R.; D’Andrea, G.; Dainese, E.; Cecconi, S.; et al. Bisphenol A Deranges the Endocannabinoid System of Primary Sertoli Cells with an Impact on Inhibin B Production. Int. J. Mol. Sci. 2020, 21, 8986. https://doi.org/10.3390/ijms21238986

AMA Style

Rossi G, Dufrusine B, Lizzi AR, Luzi C, Piccoli A, Fezza F, Iorio R, D’Andrea G, Dainese E, Cecconi S, et al. Bisphenol A Deranges the Endocannabinoid System of Primary Sertoli Cells with an Impact on Inhibin B Production. International Journal of Molecular Sciences. 2020; 21(23):8986. https://doi.org/10.3390/ijms21238986

Chicago/Turabian Style

Rossi, Gianna, Beatrice Dufrusine, Anna Rita Lizzi, Carla Luzi, Alessandra Piccoli, Filomena Fezza, Roberto Iorio, Gabriele D’Andrea, Enrico Dainese, Sandra Cecconi, and et al. 2020. "Bisphenol A Deranges the Endocannabinoid System of Primary Sertoli Cells with an Impact on Inhibin B Production" International Journal of Molecular Sciences 21, no. 23: 8986. https://doi.org/10.3390/ijms21238986

APA Style

Rossi, G., Dufrusine, B., Lizzi, A. R., Luzi, C., Piccoli, A., Fezza, F., Iorio, R., D’Andrea, G., Dainese, E., Cecconi, S., & Maccarrone, M. (2020). Bisphenol A Deranges the Endocannabinoid System of Primary Sertoli Cells with an Impact on Inhibin B Production. International Journal of Molecular Sciences, 21(23), 8986. https://doi.org/10.3390/ijms21238986

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