Simon Roelens

Uptake and tissue-specific distribution of selected polychlorinated biphenyls in developing chicken embryos

Fertilized chicken eggs were injected with high doses of individual polychlorinated biphenyl (PCB) congeners (0.5 microg of PCB 77, 9.8 microg of PCB 153, or 10.9 microg of PCB 180) before incubation to investigate the structure-specific uptake of these compounds by the embryo and their accumulation in brain and liver tissue. In accordance with earlier publications, a gradual uptake and accumulation of these compounds was observed during the last week of embryonic development. The PCB uptake and distribution to the specific tissues did not appear to be structure dependent. Wet-weight liver PCB concentrations (18, 266, and 278 ng/g at hatching for PCB 77, PCB 153, and PCB 180, respectively) were consistently two- to fourfold higher than carcass levels (7 ng/g of PCB 77, 117 ng/g of PCB 153, and 81 ng/g of PCB 180 at hatching). Whereas liver and carcass concentrations increased exponentially between day 13 of incubation and hatching, PCB levels in brain tissue remained unaltered (range, 0.6-1.0 ng/g of PCB 77 and 8-12 ng/g of PCB 153 and PCB 180 throughout the last week of incubation). Lipid analysis of the organs suggested that the lipid composition of brain may be an important factor explaining the low PCB accumulation in this tissue.

Neurotoxicity of Polychlorinated Biphenyls (PCBs) by Disturbance of Thyroid Hormone‐Regulated Genes

Abstract: PCBs are known as neurotoxic compounds. Part of this neurotoxicity could be due to an alteration of the expression of TH‐regulated genes in brain. To identify such genes, brain protein extracts of hypo‐ and hyperthyroid as well as PCB‐treated embryos were compared by fluorescent 2D‐DIGE. In total, we observed 109 differentially expressed proteins, of which 17 differed with both PCB and hypo‐ or hyperthyroid treatment. It was found that the interaction of PCBs with the expression of TH‐regulated genes is congener‐specific and that both hyperthyroidism‐ and hypothyroidism‐related effects occur.

Role of spatiotemporal expression of iodothyronine deiodinase proteins in cerebellar cell organization.

Thyroid hormones (TH) play a crucial role in various developmental processes in all vertebrates. The expression of a number of thyroid hormone responsive genes is of critical importance in processes like cell maturation and migration. Since these genes are mostly regulated by binding of the receptor-active TH (T(3)) to the thyroid hormone receptor, the availability of this T(3) is indispensable for correct brain lamination. One important way to regulate local TH availability is via the ontogenetic changes in activating and inactivating iodothyronine deiodinases. The current study was set up to investigate the distribution of type I, type II and type III (D1, D2 and D3) iodothyronine deiodinase protein in the chicken cerebellum at two important developmental ages, namely embryonic day 18 when cerebellar cell migration is fully in progress, and 1 day posthatch, when cerebellar maturation is mostly finished. The results show that the deiodinase proteins are divergently expressed in the cerebellar cell population. D1 and D3 are expressed in the granule cells at E18, whereas D2 is found mostly in the molecular layer and the Purkinje cells at that time. One day posthatch, the expression of D1 is limited to the mature granule cells and that of D3 to the Purkinje cells exclusively, whereas D2 remains clearly present in the molecular layer. Comparison of the deiodinase protein distribution with the expression of TH-responsive proteins involved in cell migration (reelin, disabled protein 1 and tenascin-C) allows speculating about the effect of this spatiotemporal distribution pattern on cerebellar cell communicative pathways.

Regulation of Thyroid Hormone Availability by Iodothyronine Deiodinases at the Blood‐Brain Barrier in Birds

Abstract: It is accepted that type II iodothyronine deiodinase (D2) is predominantly found in brain, where it maintains homeostasis of thyroid hormone (TH) levels. The current study describes the production of a polyclonal D2 antiserum and its use in the comparison of D2 protein distribution with that of type I (D1) and type III (D3) deiodinase protein in the chicken choroid plexus (CP). Immunocytochemistry showed high D2 protein expression in the epithelial cells of the CP, whereas the D1 and D3 proteins were absent. Furthermore, dexamethasone treatment led to an upregulation of the D2 protein in these cells.

Interaction of PCBs with thyroid hormone levels and time of hatching in chicken embryos.

Abstract: The effects of polychlorinated biphenyls (PCB 77, PCB 153, and the mixture Aroclor 1242) on circulating and intracellular thyroid hormone (TH) levels were studied during chicken embryonic development. We observed no influences of PCB 153 on TH availability. Aroclor 1242 caused a transient increase in the T3 level in the cerebellum at day 16. Clear effects were only seen with PCB 77 around the period of hatching: a severely reduced TH peak, which normally coincides with the stage of internal pipping, and a considerable delay in the moment of hatching.