Journal Article

Placental Transfer of a Hydroxylated Polychlorinated Biphenyl and Effects on Fetal and Maternal Thyroid Hormone Homeostasis in the Rat

Ilonka A. T. M. Meerts, Yvonne Assink, Peter H. Cenijn, Johannes H. J. van den Berg, Bert M. Weijers, Åke Bergman, Jan H. Koeman and Abraham Brouwer

in Toxicological Sciences

Volume 68, issue 2, pages 361-371
Published in print August 2002 | ISSN: 1096-6080
Published online August 2002 | e-ISSN: 1096-0929 | DOI: http://dx.doi.org/10.1093/toxsci/68.2.361
Placental Transfer of a Hydroxylated Polychlorinated Biphenyl and Effects on Fetal and Maternal Thyroid Hormone Homeostasis in the Rat

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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% respectively 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.

Keywords: hydroxylated PCB; T3; T4; thyroid stimulating hormone; glucuronosyltransferase

Journal Article.  8628 words.  Illustrated.

Subjects: Medical Toxicology ; Toxicology (Non-medical)

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