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

Gianna Rossi, Beatrice Dufrusine, Anna Rita Lizzi, Carla Luzi, Alessandra Piccoli, Filomena Fezza, Roberto Iorio, Gabriele D’andrea, Enrico Dainese, Sandra Cecconi, Mauro Maccarrone

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number8986
Pages (from-to)1-15
Number of pages15
JournalInternational Journal of Molecular Sciences
Volume21
Issue number23
DOIs
Publication statusPublished - Dec 1 2020

Keywords

  • Endocrine disruptor
  • Inhibin B
  • Male reproduction
  • Receptor signalling
  • Spermatogenesis

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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