Identification of transcriptional changes indicative of retinoic acid receptor disruption in mouse neural progenitor cells

Sammanfattning

PFOS (pluorooctane sulfonic acid) and PCB 180 (2,2′,3,4,4′,5,5′-heptachlorobiphenyl) are endocrine-disrupting chemicals (EDCs) ubiquitously found throughout the environment, given their persistence and extreme long biological half-life. PFOS and PCB 180 are predicted to disrupt retinoic acid receptor (Rar) signaling, interfering with important events of brain development, including neural differentiation and proliferation. Despite accumulating reports on the adversities of these EDCs, studies on the underlying mechanism continue to be largely unknown. The aim of this study was to validate transcriptional markers predictive of Rar disruption and to assess whether the same effects are induced by PFOS and PCB 180 exposure. Murine neural progenitor C17.2 cells were employed to mimic the developing brain. The cells were exposed to increasing nanomolar concentrations (nM) of Rar (ant)agonist, PFOS, and PCB 180. Interestingly, of all the transcriptional markers investigated, Ccn2 (cellular communication network factor 2), Il18 (Interleukin -18), and Ntn1(Netrin 1) were significantly altered by the Rar agonist (P< 0.05). Likewise, the expression of Il18 and Ntn1 was also altered by developmental exposure to PFOS and PCB 180. Altogether, these findings indicate that Il18 and Ntn1 may be promising markers for studying developmental neurotoxicity induced by disruption of the retinoic acid pathway.