Staff Publications

Staff Publications

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    'Staff publications' is the digital repository of Wageningen University & Research

    'Staff publications' contains references to publications authored by Wageningen University staff from 1976 onward.

    Publications authored by the staff of the Research Institutes are available from 1995 onwards.

    Full text documents are added when available. The database is updated daily and currently holds about 240,000 items, of which 72,000 in open access.

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Record number 317582
Title Placental transfer of a hydroxylated polychlorinated biphenyl and effects on fetal and maternal thyroid hormone homeostasis in the rat
Author(s) Meerts, I.A.T.M.; Assin, Y.; Cenijn, P.H.; Berg, J.J.J. van den; Weijers, B.M.; Bergman, A.; Koeman, J.H.; Brouwer, A.
Source Toxicological sciences 68 (2002). - ISSN 1096-6080 - p. 361 - 371.
DOI http://dx.doi.org/10.1093/toxsci/68.2.361
Department(s) Sub-department of Toxicology
WIMEK
Publication type Refereed Article in a scientific journal
Publication year 2002
Abstract Earlier studies at our laboratory indicated that several hydroxylated polychlorinated biphenyls (OH-PCBs) detected in human blood could specifically inhibit thyroxine (T4) transport by competitive binding to the thyroid hormone transport protein transthyretin (TTR) in vitro. In the present study we investigated the effects of prenatal exposure to 5 mg/kg body weight of [14C]-labeled or unlabeled 4-OH-2,3,3',4',5-pentachlorobiphenyl (4-OH-CB107), one of the major metabolites of PCBs detected in human blood, from gestation days (GD) 10 to 16 on thyroid hormone status and metabolism in pregnant rats and their fetuses at GD 17 and GD 20. 4-OH-CB107 is a metabolite of both 2,3,3',4,4'-pentachlorobiphenyl (CB-105) and 2,3',4,4',5-pentachlorobiphenyl (CB-118). We were able to show the accumulation of 4-OH-CB107 in the fetal compartment. The fetal/maternal ratios at GD 20 in liver, cerebellum, and plasma were 11.0, 2.6, and 1.2, respectively. The 14C-4-OH-CB107-derived radioactivity in plasma was bound to TTR in both dams and fetuses. Fetal plasma TT4 and FT4 levels were significantly decreased at GD 17 and GD 20 (89 and 41␛espectively at GD 20). Fetal thyroid stimulating hormone levels were increased by 124 at GD 20. The T4 concentrations in fetal forebrain homogenates at GD20 were reduced by 35°but no effects could be detected on brain T3 concentrations. The deiodination of T4 to T3 was significantly increased in fetal forebrain homogenates at GD 17, and unaltered at GD 20. In addition, no alterations were observed in maternal and fetal hepatic T4-UDP-glucuronosyltransferase activity, type I deiodinase activity, and EROD activity. In conclusion, exposure of pregnant rats to 4-OH-CB107 results in the distribution of the compound in the maternal and fetal compartment, which is probably caused by the binding of the PCB metabolite to TTR. Consequently, TT4 levels in fetal plasma and brain samples were reduced. Despite reductions in fetal brain T4 levels, the active hormone (T3) in fetal brains remained unaffected.
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