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CONCLUSION: Our findings suggest that in contrast to wild-type mNPCs, hNPCs were protected against polycyclic aromatic hydrocarbon-induced DNT because of an absence of AhR.
To investigate potential species-specific differences, we employed comparative in vitro test systems for brain development based on neurosphere cultures from human and mouse neural progenitor cells (hNPCs and mNPCs, respectively).
hNPCs used in this study were purchased from Lonza Verviers SPRL (Verviers, Belgium), Data presented in this study are based on experiments conducted on hNPCs obtained from a single male at gestational week 16.
Both hNPCs and mNPCs were cultured in proliferation medium [DMEM and Hams F12 (3:1) supplemented with B27 (Invitrogen GmBH, Karlsruhe, Germany), 20 ng/mL epidermal growth factor (EGF; Biosource, Karlsruhe, Germany), 20 ng/mL recombinant human fibroblast growth factor (FGF; R&D Systems, Wiesbaden-Nordenstadt, Germany), 100 U/mL penicillin, and 100 [micro]g/ml.
AhR agonism or antagonism does not cause cytotoxicity in hNPCs and mNPCs.
Proliferation of mNPCs, but not hNPCs, is inhibited by AhR blockage.
In contrast, BDE-47 and BDE-99 increased nestin expression 4- and 5-fold, showing that PBDEs delay differentiation of hNPCs (Figure 3B).
In contrast, NH-3 inhibited migration of hNPCs to 735.2 [+ or -]7-2 [micro]m, (78.2 [+ or -] 1.8% of controls).
PBDEs accumulate in hNPCs. Exposure of hNPCs to 1 [micro]M (14) C-BDE-47 for 7 days resulted in a cellular concentration of 61.16 [+ or -] 6.34 [micro]M, which equals an accumulation factor of GO.
To shed light onto the effects caused by PBDE exposure in human developing brain cells, we studied their effects on the development of hNPCs in vitro.
PBDEs (0.1-10 [micro]M) are not cytotoxic for proliferating or differentiating hNPCs over a period of 2 weeks, as we demonstrated by different, independent methods [see Supplemental Material, Figures 1 and 2 (doi: 10.1289/ehp.0901435)].
In contrast to proliferation, both investigated PBDE congeners inhibit migration and differentiation of hNPCs significantly in a concentration-dependent manner (Figures 1 and 2).
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