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.

Rossi, G., Dufrusine, B., Lizzi, A.r., Luzi, C., Piccoli, A., Fezza, F., 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(23), 1-15 [10.3390/ijms21238986].

Bisphenol a deranges the endocannabinoid system of primary sertoli cells with an impact on inhibin b production

Fezza F.;Maccarrone M.
2020-01-01

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.
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore BIO/10
English
Cell Survival
Endocrine disruptor
Inhibin B
Male reproduction
Receptor signalling
Spermatogenesis
Animals
Benzhydryl Compounds
Cells, Cultured
Endocannabinoids
Gene Expression Regulation
Inhibins
Male
Mice
Phenols
RNA, Messenger
Receptors, Cannabinoid
Sertoli Cells
Transferrin
Rossi, G., Dufrusine, B., Lizzi, A.r., Luzi, C., Piccoli, A., Fezza, F., 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(23), 1-15 [10.3390/ijms21238986].
Rossi, G; Dufrusine, B; Lizzi, Ar; Luzi, C; Piccoli, A; Fezza, F; Iorio, R; D'Andrea, G; Dainese, E; Cecconi, S; Maccarrone, M
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/296090
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