Login / Signup

Disruption of neurosteroid synthesis and release by tris(2,3-dibromopropyl)isocyanurate in primary mouse cortical astrocytes in vitro.

Konrad A SzychowskiBartosz Skóra
Published in: Journal of applied toxicology : JAT (2023)
Neurosteroidogenesis in astrocytes is crucial for the proper development and functioning of the brain. During this process, key neurohormones such as progesterone (P 4 ), testosterone (T), and estradiol (E 2 ) are produced. Proper production and release of neurosteroids can be affected by substances referred to as endocrine-disrupting compounds (EDCs). Tris-(2,3-dibromopropyl)isocyanurate (TBC) is a representative of novel brominated flame retardants used to stop ignition or reduce fire-related property damage to plastics, polyolefin, polyphenyl alkene, unsaturated polyester, synthetic rubber, and fibers. Interestingly, previous studies have shown that TBC can enhance the proliferation of estradiol-sensitive breast cancers in vitro, which suggests that TBC has EDC properties. Therefore, given the suspected endocrine-disrupting properties of TBC, the aim of the present study was to determine the impact of TBC on the neurosteroid (P 4 , T, and E 2 ) production and secretion as well as the mRNA expression of key enzymes involved in its production in mouse astrocytes in vitro. Our paper shows that TBC increases P 4 production with a strong decrease in T production, which is accompanied by a decrease in Cyp17a1 mRNA expression, that is, the main enzyme metabolizing P 4 to T. Moreover, TBC in both studied concentrations increases P 4 secretion in the culture medium. Finally, our studies have demonstrated an increase in the expression of Cyp19a1 mRNA, an enzyme metabolizing T to E 2 , with a simultaneous increase in the amount of E 2 in cells. Our data clearly show that TBC in an in vitro environment acts as EDCs, which may lead to serious consequences for the proper development and functioning of the brain.
Keyphrases
  • white matter
  • resting state
  • oxidative stress
  • multiple sclerosis
  • machine learning
  • electronic health record
  • brain injury
  • functional connectivity